@article{MTMT:3320653,
	title = {TRPV1 antagonists that cause hypothermia, instead of hyperthermia, in rodents: compounds' pharmacological profiles, in vivo targets, thermoeffectors recruited, and implications for drug development},
	url = {https://m2.mtmt.hu/api/publication/3320653},
	author = {Garami, András and Pákai, Eszter and McDonald, HA and Reilly, RM and Gomtsyan, A and Corrigan, JJ and Pintér, Erika and Zhu, DXD and Lehto, SG and Gavva, NR and Kym, PR and Romanovsky, AA},
	doi = {10.1111/apha.13038},
	journal-iso = {ACTA PHYSIOL},
	journal = {ACTA PHYSIOLOGICA},
	volume = {223},
	unique-id = {3320653},
	issn = {1748-1708},
	abstract = {AIM: Thermoregulatory side effects hinder the development of transient receptor potential vanilloid-1 (TRPV1) antagonists as new painkillers. While many antagonists cause hyperthermia, a well-studied effect, some cause hypothermia. The mechanisms of this hypothermia are unknown and were studied herein. METHODS: Two hypothermia-inducing TRPV1 antagonists, the newly synthesized A-1165901 and the known AMG7905, were used in physiological experiments in rats and mice. Their pharmacological profiles against rat TRPV1 were studied in vitro. RESULTS: Administered peripherally, A-1165901 caused hypothermia in rats by either triggering tail-skin vasodilation (at thermoneutrality) or inhibiting thermogenesis (in the cold). A-1165901-induced hypothermia did not occur in rats with desensitized (by an intraperitoneal dose of the TRPV1 agonist resiniferatoxin) sensory abdominal nerves. The hypothermic responses to A-1165901 and AMG7905 (administered intragastrally or intraperitoneally) were absent in Trpv1(-/-) mice, even though both compounds evoked pronounced hypothermia in Trpv1(+/+) mice. In vitro, both A-1165901 and AMG7905 potently potentiated TRPV1 activation by protons, while potently blocking channel activation by capsaicin. CONCLUSIONS: TRPV1 antagonists cause hypothermia by an on-target action: on TRPV1 channels on abdominal sensory nerves. These channels are tonically activated by protons and drive the reflectory inhibition of thermogenesis and tail-skin vasoconstriction. Those TRPV1 antagonists that cause hypothermia further inhibit these cold-defences, thus decreasing body temperature. SIGNIFICANCE: TRPV1 antagonists are highly unusual in that they can cause both hyper- and hypothermia by modulating the same mechanism. For drug development this means that both side effects can be dealt with simultaneously, by minimizing these compounds' interference with TRPV1 activation by protons. This article is protected by copyright. All rights reserved.},
	year = {2018},
	eissn = {1748-1716},
	orcid-numbers = {Garami, András/0000-0003-2493-0571; Pintér, Erika/0000-0001-9898-632X}
}

@article{MTMT:30323940,
	title = {Fever and hypothermia in systemic inflammation.},
	url = {https://m2.mtmt.hu/api/publication/30323940},
	author = {Garami, András and Steiner, Alexandre A and Romanovsky, Andrej A},
	doi = {10.1016/B978-0-444-64074-1.00034-3},
	journal-iso = {HANDB CLIN NEUROL},
	journal = {HANDBOOK OF CLINICAL NEUROLOGY},
	volume = {157},
	unique-id = {30323940},
	issn = {0072-9752},
	abstract = {Systemic inflammation-associated syndromes (e.g., sepsis and septic shock) often have high mortality and remain a challenge in emergency medicine. Systemic inflammation is usually accompanied by changes in body temperature: fever or hypothermia. In animal studies, systemic inflammation is often modeled by administering bacterial lipopolysaccharide, which triggers autonomic and behavioral thermoeffector responses and causes either fever or hypothermia, depending on the dose and ambient temperature. Fever and hypothermia are regulated changes of body temperature, which correspond to mild and severe forms of systemic inflammation, respectively. Mediators of fever and hypothermia are called endogenous pyrogens and cryogens; they are produced when the innate immune system recognizes an infectious pathogen. Upon an inflammatory challenge, hepatic and pulmonary macrophages (and later brain endothelial cells) start to release lipid mediators, of which prostaglandin (PG) E2 plays the key role, and cytokines. Blood PGE2 enters the brain and triggers fever. At later stages of fever, PGE2 synthesized within the blood-brain barrier maintains fever. In both cases, PGE2 is synthesized by cyclooxygenase-2 and microsomal PGE2synthase-1. Mediators of hypothermia are not well established. Both fever and hypothermia are beneficial host defense responses. Based on evidence from studies in laboratory animals and clinical trials in humans, fever is beneficial for fighting mild infection. Based mainly on animal studies, hypothermia is beneficial in severe systemic inflammation and infection.},
	keywords = {NEUROPEPTIDE; THERMOREGULATION; ENDOTOXIN; PROSTAGLANDIN; Sepsis; shock; CYCLOOXYGENASE; body temperature; LPS; SIRS; sickness syndrome},
	year = {2018},
	eissn = {2212-4152},
	pages = {565-597},
	orcid-numbers = {Garami, András/0000-0003-2493-0571}
}

@article{MTMT:3401717,
	title = {Manipulating transient receptor potential vanilloid 1 antagonists: How to cool down a hot molecule?},
	url = {https://m2.mtmt.hu/api/publication/3401717},
	author = {Islas, LD and Szállási, Árpád},
	doi = {10.1111/apha.13088},
	journal-iso = {ACTA PHYSIOL},
	journal = {ACTA PHYSIOLOGICA},
	volume = {223},
	unique-id = {3401717},
	issn = {1748-1708},
	year = {2018},
	eissn = {1748-1716}
}

@article{MTMT:3365563,
	title = {Therapeutic Whole-Body Hypothermia Reduces Death in Severe Traumatic Brain Injury if the Cooling Index Is Sufficiently High: Meta-Analyses of the Effect of Single Cooling Parameters and Their Integrated Measure},
	url = {https://m2.mtmt.hu/api/publication/3365563},
	author = {Pótóné Oláh, Emőke and Pótó, László and Hegyi, Péter and Szabó, Imre and Hartmann, Petra and Varjú-Solymár, Margit and Pétervári, Erika and Balaskó, Márta and Habon, Tamás and Rumbus, Zoltán and Tenk, Judit and Rostás, Ildikó and Weinberg, J and Romanovsky, AA and Garami, András},
	doi = {10.1089/neu.2018.5649},
	journal-iso = {J NEUROTRAUM},
	journal = {JOURNAL OF NEUROTRAUMA},
	volume = {35},
	unique-id = {3365563},
	issn = {0897-7151},
	abstract = {Therapeutic hypothermia was investigated repeatedly as a tool to improve the outcome of severe traumatic brain injury (TBI), but previous clinical trials and meta-analyses found contradictory results. We aimed to determine the effectiveness of therapeutic whole-body hypothermia on the mortality of adult patients with severe TBI by using a novel approach of meta-analysis. We searched the PubMed, EMBASE, and Cochrane Library databases from inception to February 2017. The identified human studies were evaluated regarding statistical, clinical, and methodological designs to ensure inter-study homogeneity. We extracted data on TBI severity, body temperature, mortality, and cooling parameters; then we calculated the cooling index, an integrated measure of therapeutic hypothermia. Forest plot of all identified studies showed no difference in the outcome of TBI between cooled and not cooled patients, but inter-study heterogeneity was high. On the contrary, by meta-analysis of RCTs which were homogenous with regards to statistical, clinical designs and precisely reported the cooling protocol, we showed decreased odds ratio for mortality in therapeutic hypothermia compared to no cooling. As independent factors, milder and longer cooling, and rewarming at < 0.25 degrees C/h were associated with better outcome. Therapeutic hypothermia was beneficial only if the cooling index (measure of combination of cooling parameters) was sufficiently high. We conclude that high methodological and statistical inter-study heterogeneity could underlie the contradictory results obtained in previous studies. By analyzing methodologically homogenous studies, we show that cooling improves the outcome of severe TBI and this beneficial effect depends on certain cooling parameters and on their integrated measure, the cooling index.},
	year = {2018},
	eissn = {1557-9042},
	pages = {2407-2417},
	orcid-numbers = {Hegyi, Péter/0000-0003-0399-7259; Hartmann, Petra/0000-0002-4746-9792; Varjú-Solymár, Margit/0000-0001-6667-6263; Pétervári, Erika/0000-0002-3673-8491; Habon, Tamás/0000-0002-4816-857X; Garami, András/0000-0003-2493-0571}
}

@article{MTMT:3338655,
	title = {The Neurokinin-1 Receptor Contributes to the Early Phase of Lipopolysaccharide-Induced Fever via Stimulation of Peripheral Cyclooxygenase-2 Protein Expression in Mice},
	url = {https://m2.mtmt.hu/api/publication/3338655},
	author = {Pákai, Eszter and Tékus, Valéria and Zsiboras, C and Rumbus, Zoltán and Pótóné Oláh, Emőke and Kéringer, Patrik and Khidhir, N and Mátics, Róbert and Deres, László and Takács-Ördög, Katalin and Szentes, Nikolett and Pohóczky, Krisztina and Kemény, Ágnes and Hegyi, Péter and Pintér, Erika and Garami, András},
	doi = {10.3389/fimmu.2018.00166},
	journal-iso = {FRONT IMMUNOL},
	journal = {FRONTIERS IN IMMUNOLOGY},
	volume = {9},
	unique-id = {3338655},
	issn = {1664-3224},
	year = {2018},
	eissn = {1664-3224},
	orcid-numbers = {Pohóczky, Krisztina/0000-0003-0385-5162; Kemény, Ágnes/0000-0002-4523-3938; Hegyi, Péter/0000-0003-0399-7259; Pintér, Erika/0000-0001-9898-632X; Garami, András/0000-0003-2493-0571}
}

@article{MTMT:3255863,
	title = {Transient Receptor Potential Vanilloid 1 Antagonists Prevent Anesthesia-induced Hypothermia and Decrease Postincisional Opioid Dose Requirements in Rodents.},
	url = {https://m2.mtmt.hu/api/publication/3255863},
	author = {Garami, András and Ibrahim, M and Gilbraith, K and Khanna, R and Pákai, Eszter and Mikó, Alexandra and Pintér, Erika and Romanovsky, AA and Porreca, F and Patwardhan, AM},
	doi = {10.1097/ALN.0000000000001812},
	journal-iso = {ANESTHESIOLOGY},
	journal = {ANESTHESIOLOGY},
	volume = {127},
	unique-id = {3255863},
	issn = {0003-3022},
	abstract = {BACKGROUND: Intraoperative hypothermia and postoperative pain control are two important clinical challenges in anesthesiology. Transient receptor potential vanilloid 1 has been implicated both in thermoregulation and pain. Transient receptor potential vanilloid 1 antagonists were not advanced as analgesics in humans in part due to a side effect of hyperthermia. This study tested the hypothesis that a single, preincision injection of a transient receptor potential vanilloid 1 antagonist could prevent anesthesia-induced hypothermia and decrease the opioid requirement for postsurgical hypersensitivity. METHODS: General anesthesia was induced in rats and mice with either isoflurane or ketamine, and animals were treated with transient receptor potential vanilloid 1 antagonists (AMG 517 or ABT-102). The core body temperature and oxygen consumption were monitored during anesthesia and the postanesthesia period. The effect of preincision AMG 517 on morphine-induced reversal of postincision hyperalgesia was evaluated in rats. RESULTS: AMG 517 and ABT-102 dose-dependently prevented general anesthesia-induced hypothermia (mean +/- SD; from 1.5 degrees +/- 0.1 degrees C to 0.1 degrees +/- 0.1 degrees C decrease; P < 0.001) without causing hyperthermia in the postanesthesia phase. Isoflurane-induced hypothermia was prevented by AMG 517 in wild-type but not in transient receptor potential vanilloid 1 knockout mice (n = 7 to 11 per group). The prevention of anesthesia-induced hypothermia by AMG 517 involved activation of brown fat thermogenesis with a possible contribution from changes in vasomotor tone. A single preincision dose of AMG 517 decreased the morphine dose requirement for the reduction of postincision thermal (12.6 +/- 3.0 vs. 15.6 +/- 1.0 s) and mechanical (6.8 +/- 3.0 vs. 9.5 +/- 3.0 g) withdrawal latencies. CONCLUSIONS: These studies demonstrate that transient receptor potential vanilloid 1 antagonists prevent anesthesia-induced hypothermia and decrease opioid dose requirements for the reduction of postincisional hypersensitivity in rodents.},
	year = {2017},
	eissn = {1528-1175},
	pages = {813-823},
	orcid-numbers = {Garami, András/0000-0003-2493-0571; Pintér, Erika/0000-0001-9898-632X}
}

@article{MTMT:3401720,
	title = {TRPV1: A Potential Therapeutic Target in Type 2 Diabetes and Comorbidities?},
	url = {https://m2.mtmt.hu/api/publication/3401720},
	author = {Gram, DX and Holst, JJ and Szállási, Árpád},
	doi = {10.1016/j.molmed.2017.09.005},
	journal-iso = {TRENDS MOL MED},
	journal = {TRENDS IN MOLECULAR MEDICINE},
	volume = {23},
	unique-id = {3401720},
	issn = {1471-4914},
	year = {2017},
	eissn = {1471-499X},
	pages = {1002-1013}
}

@article{MTMT:3167989,
	title = {Fever Is Associated with Reduced, Hypothermia with Increased Mortality in Septic Patients: A Meta-Analysis of Clinical Trials},
	url = {https://m2.mtmt.hu/api/publication/3167989},
	author = {Rumbus, Zoltán and Mátics, Róbert and Hegyi, Péter and Zsiboras, C and Szabó, Imre and Illés, Anita and Pétervári, Erika and Balaskó, Márta and Márta, Katalin and Mikó, Alexandra and Párniczky, Andrea and Tenk, Judit and Rostás, Ildikó and Varjú-Solymár, Margit and Garami, András},
	doi = {10.1371/journal.pone.0170152},
	journal-iso = {PLOS ONE},
	journal = {PLOS ONE},
	volume = {12},
	unique-id = {3167989},
	issn = {1932-6203},
	abstract = {BACKGROUND: Sepsis is usually accompanied by changes of body temperature (Tb), but whether fever and hypothermia predict mortality equally or differently is not fully clarified. We aimed to find an association between Tb and mortality in septic patients with meta-analysis of clinical trials. METHODS: We searched the PubMed, EMBASE, and Cochrane Controlled Trials Registry databases (from inception to February 2016). Human studies reporting Tb and mortality of patients with sepsis were included in the analyses. Average Tb with SEM and mortality rate of septic patient groups were extracted by two authors independently. RESULTS: Forty-two studies reported Tb and mortality ratios in septic patients (n = 10,834). Pearson correlation analysis revealed weak negative linear correlation (R2 = 0.2794) between Tb and mortality. With forest plot analysis, we found a 22.2% (CI, 19.2-25.5) mortality rate in septic patients with fever (Tb > 38.0 degrees C), which was higher, 31.2% (CI, 25.7-37.3), in normothermic patients, and it was the highest, 47.3% (CI, 38.9-55.7), in hypothermic patients (Tb < 36.0 degrees C). Meta-regression analysis showed strong negative linear correlation between Tb and mortality rate (regression coefficient: -0.4318; P < 0.001). Mean Tb of the patients was higher in the lowest mortality quartile than in the highest: 38.1 degrees C (CI, 37.9-38.4) vs 37.1 degrees C (CI, 36.7-37.4). CONCLUSIONS: Deep Tb shows negative correlation with the clinical outcome in sepsis. Fever predicts lower, while hypothermia higher mortality rates compared with normal Tb. Septic patients with the lowest (< 25%) chance of mortality have higher Tb than those with the highest chance (> 75%).},
	year = {2017},
	eissn = {1932-6203},
	orcid-numbers = {Hegyi, Péter/0000-0003-0399-7259; Pétervári, Erika/0000-0002-3673-8491; Márta, Katalin/0000-0002-2213-4865; Varjú-Solymár, Margit/0000-0001-6667-6263; Garami, András/0000-0003-2493-0571}
}

@inbook{MTMT:3134625,
	title = {The Role of PACAP in the Regulation of Body Temperature},
	url = {https://m2.mtmt.hu/api/publication/3134625},
	author = {Garami, András and Pákai, Eszter and Rumbus, Zoltán and Varjú-Solymár, Margit},
	booktitle = {Pituitary Adenylate Cyclase Activating Polypeptide — PACAP},
	doi = {10.1007/978-3-319-35135-3_15},
	unique-id = {3134625},
	year = {2016},
	pages = {239-257},
	orcid-numbers = {Garami, András/0000-0003-2493-0571; Varjú-Solymár, Margit/0000-0001-6667-6263}
}

@article{MTMT:2883057,
	title = {Hyperbilirubinemia exaggerates endotoxin-induced hypothermia.},
	url = {https://m2.mtmt.hu/api/publication/2883057},
	author = {Pákai, Eszter and Garami, András and Nucci, TB and Ivanov, AI and Romanovsky, AA},
	doi = {10.1080/15384101.2015.1014150},
	journal-iso = {CELL CYCLE},
	journal = {CELL CYCLE},
	volume = {14},
	unique-id = {2883057},
	issn = {1538-4101},
	abstract = {Systemic inflammation is accompanied by an increased production of reactive oxygen species (ROS) and by either fever or hypothermia (or both). To study aseptic systemic inflammation, it is often induced in rats by the intravenous administration of bacterial lipopolysaccharide (LPS). Knowing that bilirubin is a potent ROS scavenger, we compared responses to LPS between normobilirubinemic Gunn rats (heterozygous, asymptomatic; J/+) and hyperbilirubinemic Gunn rats (homozygous, jaundiced; J/J) to establish whether ROS mediate fever and hypothermia in aseptic systemic inflammation. These two genotypes correspond to undisturbed versus drastically suppressed (by bilirubin) tissue accumulation of ROS, respectively. A low dose of LPS (10 mug/kg) caused a typical triphasic fever in both genotypes, without any intergenotype differences. A high dose of LPS (1,000 mug/kg) caused a complex response consisting of early hypothermia followed by late fever. The hypothermic response was markedly exaggerated, whereas the subsequent fever response was strongly attenuated in J/J rats, as compared to J/+ rats. J/J rats also tended to respond to 1,000 mug/kg with blunted surges in plasma levels of all hepatic enzymes studied (alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase), thus suggesting an attenuation of hepatic damage. We propose that the reported exaggeration of LPS-induced hypothermia in J/J rats occurs via direct inhibition of nonshivering thermogenesis by bilirubin and possibly via a direct vasodilatatory action of bilirubin in the skin. This hypothermia-exaggerating effect might be responsible, at least in part, for the observed tendency of J/J rats to be protected from LPS-induced hepatic damage. The attenuation of the fever response to 1,000 mug/kg could be due to either direct actions of bilirubin on thermoeffectors or the ROS-scavenging action of bilirubin. However, the experiments with 10 mug/kg strongly suggest that ROS signaling is not involved in the fever response to low doses of LPS.},
	year = {2015},
	eissn = {1551-4005},
	pages = {1260-1267},
	orcid-numbers = {Garami, András/0000-0003-2493-0571}
}

@article{MTMT:2699482,
	title = {Characterization of the thermoregulatory response to pituitary adenylate cyclase-activating polypeptide in rodents},
	url = {https://m2.mtmt.hu/api/publication/2699482},
	author = {Bánki, Eszter Márta and Pákai, Eszter and Gaszner, Balázs and Zsiboras, Cs and Czett, A and Bhuddi, PRP and Hashimoto, H and Tóth, Gábor and Tamás, Andrea and Reglődi, Dóra and Garami, András},
	doi = {10.1007/s12031-014-0361-0},
	journal-iso = {J MOL NEUROSCI},
	journal = {JOURNAL OF MOLECULAR NEUROSCIENCE},
	volume = {54},
	unique-id = {2699482},
	issn = {0895-8696},
	year = {2014},
	eissn = {1559-1166},
	pages = {543-554},
	orcid-numbers = {Gaszner, Balázs/0000-0003-2830-2732; Tóth, Gábor/0000-0002-3604-4385; Garami, András/0000-0003-2493-0571}
}

@article{MTMT:2564840,
	title = {Transient receptor potential channel ankyrin-1 is not a cold sensor for autonomic thermoregulation in rodents.},
	url = {https://m2.mtmt.hu/api/publication/2564840},
	author = {de Oliveira, C and Garami, András and Lehto, SG and Pákai, Eszter and Tékus, Valéria and Pohóczky, Krisztina and Youngblood, BD and Wang, W and Kort, ME and Kym, PR and Pintér, Erika and Gavva, NR and Romanovsky, AA},
	doi = {10.1523/JNEUROSCI.5387-13.2014},
	journal-iso = {J NEUROSCI},
	journal = {JOURNAL OF NEUROSCIENCE},
	volume = {34},
	unique-id = {2564840},
	issn = {0270-6474},
	abstract = {The rodent transient receptor potential ankyrin-1 (TRPA1) channel has been hypothesized to serve as a temperature sensor for thermoregulation in the cold. We tested this hypothesis by using deletion of the Trpa1 gene in mice and pharmacological blockade of the TRPA1 channel in rats. In both Trpa1(-/-) and Trpa1(+/+) mice, severe cold exposure (8 degrees C) resulted in decreases of skin and deep body temperatures to approximately 8 degrees C and 13 degrees C, respectively, both temperatures being below the reported 17 degrees C threshold temperature for TRPA1 activation. Under these conditions, Trpa1(-/-) mice had the same dynamics of body temperature as Trpa1(+/+) mice and showed no weakness in the tail skin vasoconstriction response or thermogenic response to cold. In rats, the effects of pharmacological blockade were studied by using two chemically unrelated TRPA1 antagonists: the highly potent and selective compound A967079, which had been characterized earlier, and the relatively new compound 43 ((4R)-1,2,3,4-tetrahydro-4-[3-(3-methoxypropoxy)phenyl]-2-thioxo-5H-indeno[1,2-d] pyrimidin-5-one), which we further characterized in the present study and found to be highly potent (IC50 against cold of approximately 8 nm) and selective. Intragastric administration of either antagonist at 30 mg/kg before severe (3 degrees C) cold exposure did not affect the thermoregulatory responses (deep body and tail skin temperatures) of rats, even though plasma concentrations of both antagonists well exceeded their IC50 value at the end of the experiment. In the same experimental setup, blocking the melastatin-8 (TRPM8) channel with AMG2850 (30 mg/kg) attenuated cold-defense mechanisms and led to hypothermia. We conclude that TRPA1 channels do not drive autonomic thermoregulatory responses to cold in rodents.},
	year = {2014},
	eissn = {1529-2401},
	pages = {4445-4452},
	orcid-numbers = {Garami, András/0000-0003-2493-0571; Pohóczky, Krisztina/0000-0003-0385-5162; Pintér, Erika/0000-0001-9898-632X}
}

@article{MTMT:2745196,
	title = {Body temperature. Its regulation in framework of energy balance},
	url = {https://m2.mtmt.hu/api/publication/2745196},
	author = {Garami, András and Székely, Miklós},
	doi = {10.4161/temp.29060},
	journal-iso = {TEMPERATURE},
	journal = {TEMPERATURE},
	volume = {1},
	unique-id = {2745196},
	issn = {2332-8940},
	year = {2014},
	eissn = {2332-8959},
	pages = {28-29},
	orcid-numbers = {Garami, András/0000-0003-2493-0571}
}

@article{MTMT:2745229,
	title = {The short- and long-term effects of food intake on thermogenesis},
	url = {https://m2.mtmt.hu/api/publication/2745229},
	author = {Simon, Armbruszt and Garami, András},
	doi = {10.4161/temp.29733},
	journal-iso = {TEMPERATURE},
	journal = {TEMPERATURE},
	volume = {1},
	unique-id = {2745229},
	issn = {2332-8940},
	year = {2014},
	eissn = {2332-8959},
	pages = {96-96},
	orcid-numbers = {Garami, András/0000-0003-2493-0571}
}

@article{MTMT:1852946,
	title = {Pharmacological Blockade of the Cold Receptor TRPM8 Attenuates Autonomic and Behavioral Cold Defenses and Decreases Deep Body Temperature},
	url = {https://m2.mtmt.hu/api/publication/1852946},
	author = {Almeida, MC and Hew-Butler, T and Soriano, RN and Rao, S and Wang, W and Wang, J and Tamayo, N and Oliveira, DL and Nucci, TB and Aryal, P and Garami, András and Bautista, D and Gavva, NR and Romanovsky, AA},
	doi = {10.1523/JNEUROSCI.5606-11.2012},
	journal-iso = {J NEUROSCI},
	journal = {JOURNAL OF NEUROSCIENCE},
	volume = {32},
	unique-id = {1852946},
	issn = {0270-6474},
	abstract = {We studied N-(2-aminoethyl)-N-(4-(benzyloxy)-3-methoxybenzyl)thiophene-2-carboxamide hydrochloride (M8-B), a selective and potent antagonist of the transient receptor potential melastatin-8 (TRPM8) channel. In vitro, M8-B blocked cold-induced and TRPM8-agonist-induced activation of rat, human, and murine TRPM8 channels, including those on primary sensory neurons. In vivo, M8-B decreased deep body temperature (T(b)) in Trpm8(+/+) mice and rats, but not in Trpm8(-/-) mice, thus suggesting an on-target action. Intravenous administration of M8-B was more effective in decreasing T(b) in rats than intrathecal or intracerebroventricular administration, indicating a peripheral action. M8-B attenuated cold-induced c-Fos expression in the lateral parabrachial nucleus, thus indicating a site of action within the cutaneous cooling neural pathway to thermoeffectors, presumably on sensory neurons. A low intravenous dose of M8-B did not affect T(b) at either a constantly high or a constantly low ambient temperature (T(a)), but the same dose readily decreased T(b) if rats were kept at a high T(a) during the M8-B infusion and transferred to a low T(a) immediately thereafter. These data suggest that both a successful delivery of M8-B to the skin (high cutaneous perfusion) and the activation of cutaneous TRPM8 channels (by cold) are required for the hypothermic action of M8-B. At tail-skin temperatures <23 degrees C, the magnitude of the M8-B-induced decrease in T(b) was inversely related to skin temperature, thus suggesting that M8-B blocks thermal (cold) activation of TRPM8. M8-B affected all thermoeffectors studied (thermopreferendum, tail-skin vasoconstriction, and brown fat thermogenesis), thus suggesting that TRPM8 is a universal cold receptor in the thermoregulation system.},
	year = {2012},
	eissn = {1529-2401},
	pages = {2086-2099},
	orcid-numbers = {Garami, András/0000-0003-2493-0571}
}

@article{MTMT:1816326,
	title = {Aging reverses the role of the transient receptor potential vanilloid-1 channel in systemic inflammation from anti-inflammatory to proinflammatory.},
	url = {https://m2.mtmt.hu/api/publication/1816326},
	author = {Wanner, SP and Garami, András and Pákai, Eszter and Oliveira, DL and Gavva, NR and Coimbra, CC and Romanovsky, AA},
	doi = {10.4161/cc.11.2.18772},
	journal-iso = {CELL CYCLE},
	journal = {CELL CYCLE},
	volume = {11},
	unique-id = {1816326},
	issn = {1538-4101},
	abstract = {Studies in young rodents have shown that the transient receptor potential vanilloid-1 (TRPV1) channel plays a suppressive role in the systemic inflammatory response syndrome (SIRS) by inhibiting production of tumor necrosis factor (TNF)alpha and possibly by other mechanisms. We asked whether the anti-inflammatory role of TRPV1 changes with age. First, we studied the effect of AMG517, a selective and potent TRPV1 antagonist, on aseptic, lipopolysaccharide (LPS)-induced SIRS in young (12 wk) mice. In agreement with previous studies, AMG517 increased LPS-induced mortality in the young. We then studied the effects of TRPV1 antagonism (AMG517 or genetic deletion of TRPV1) on SIRS in middle-aged (43-44 wk) mice. Both types of TRPV1 antagonism delayed and decreased LPS-induced mortality, indicating a reversal of the anti-inflammatory role of TRPV1 with aging. In addition, deletion of TRPV1 decreased the serum TNFalpha response to LPS, suggesting that the suppressive control of TRPV1 on TNFalpha production is also reversed with aging. In contrast to aseptic SIRS, polymicrobial sepsis (induced by cecal ligation and puncture) caused accelerated mortality in aged TRPV1-deficient mice as compared with wild-type littermates. The recovery of TRPV1-deficient mice from hypothermia associated with the cecal ligation and puncture procedure was delayed. Hence, the reversal of the anti-inflammatory role of TRPV1 found in the aged and their decreased systemic inflammatory response are coupled with suppressed defense against microbial infection. These results caution that TRPV1 antagonists, widely viewed as new-generation painkillers, may decrease the resistance of older patients to infection and sepsis.},
	year = {2012},
	eissn = {1551-4005},
	pages = {343-349},
	orcid-numbers = {Garami, András/0000-0003-2493-0571}
}

@article{MTMT:1437734,
	title = {Thermoregulatory phenotype of the trpv1 knockout mouse: thermoeffector dysbalance with hyperkinesis.},
	url = {https://m2.mtmt.hu/api/publication/1437734},
	author = {Garami, András and Pákai, Eszter and Oliveira, DL and Steiner, AA and Wanner, SP and Almeida, MC and Lesnikov, VA and Gavva, NR and Romanovsky, AA},
	doi = {10.1523/JNEUROSCI.4671-10.2011},
	journal-iso = {J NEUROSCI},
	journal = {JOURNAL OF NEUROSCIENCE},
	volume = {31},
	unique-id = {1437734},
	issn = {0270-6474},
	abstract = {This study aimed at determining the thermoregulatory phenotype of mice lacking transient receptor potential vanilloid-1 (TRPV1) channels. We used Trpv1 knockout (KO) mice and their genetically unaltered littermates to study diurnal variations in deep body temperature (T(b)) and thermoeffector activities under basal conditions, as well as thermoregulatory responses to severe heat and cold. Only subtle alterations were found in the basal T(b) of Trpv1 KO mice or in their T(b) responses to thermal challenges. The main thermoregulatory abnormality of Trpv1 KO mice was a different pattern of thermoeffectors used to regulate T(b). On the autonomic side, Trpv1 KO mice were hypometabolic (had a lower oxygen consumption) and hypervasoconstricted (had a lower tail skin temperature). In agreement with the enhanced skin vasoconstriction, Trpv1 KO mice had a higher thermoneutral zone. On the behavioral side, Trpv1 KO mice preferred a lower ambient temperature and expressed a higher locomotor activity. Experiments with pharmacological TRPV1 agonists (resiniferatoxin and anandamide) and a TRPV1 antagonist (AMG0347) confirmed that TRPV1 channels located outside the brain tonically inhibit locomotor activity. With age (observed for up to 14 months), the body mass of Trpv1 KO mice exceeded that of controls, sometimes approaching 60 g. In summary, Trpv1 KO mice possess a distinct thermoregulatory phenotype, which is coupled with a predisposition to age-associated overweight and includes hypometabolism, enhanced skin vasoconstriction, decreased thermopreferendum, and hyperkinesis. The latter may be one of the primary deficiencies in Trpv1 KO mice. We propose that TRPV1-mediated signals from the periphery tonically suppress the general locomotor activity.},
	year = {2011},
	eissn = {1529-2401},
	pages = {1721-1733},
	orcid-numbers = {Garami, András/0000-0003-2493-0571}
}

@article{MTMT:1436909,
	title = {Central alpha-MSH infusion in rats: disparate anorexic vs. metabolic changes with aging.},
	url = {https://m2.mtmt.hu/api/publication/1436909},
	author = {Pétervári, Erika and Szabad, AO and Soós, Szilvia and Garami, András and Székely, Miklós and Balaskó, Márta},
	doi = {10.1016/j.regpep.2010.10.002},
	journal-iso = {REGUL PEPTIDES},
	journal = {REGULATORY PEPTIDES},
	volume = {166},
	unique-id = {1436909},
	issn = {0167-0115},
	abstract = {Changes of the anorexigenic and hypermetabolic components of the overall catabolic effect of alpha-MSH were studied in rats as a function of age. In male Wistar rats a 7 day-long intracerebroventricular infusion of alpha-MSH suppressed food intake and caused a fall in body weight in 2 and 3-4 month-old (young) groups, but it was most effective in the 24 month-old group and had hardly any effect in the 12 month-old (middle-aged) animals. In contrast, metabolic rate as well as biotelemetric measurements of core temperature and heart rate revealed the most pronounced hypermetabolic effects of such infusions at age 12 months. The hypermetabolic effect was still high in the oldest group, but low in the younger groups. In conclusion: Changes of the anorexigenic and hypermetabolic effects in the course of aging are not concordant. The overall catabolic activity of alpha-MSH is smallest in the middle-aged and highest in the oldest group.},
	year = {2011},
	eissn = {1873-1686},
	pages = {105-111},
	orcid-numbers = {Pétervári, Erika/0000-0002-3673-8491; Garami, András/0000-0003-2493-0571}
}

@article{MTMT:1577325,
	title = {Hyperactive when young, hypoactive and overweight when aged: Connecting the dots in the story about locomotor activity, body mass, and aging in Trpv1 knockout mice},
	url = {https://m2.mtmt.hu/api/publication/1577325},
	author = {Wanner, SP and Garami, András and Romanovsky, AA},
	doi = {10.18632/aging.100306},
	journal-iso = {AGING-US},
	journal = {AGING-US},
	volume = {3},
	unique-id = {1577325},
	issn = {1945-4589},
	abstract = {We have recently found that, at a young age, transient receptor 
		potential vanilloid-1 (Trpv1) knockout ((-)/(-)) mice have a 
		higher locomotor activity than their wild-type littermates 
		((+)/(+)). We have also found that, with age, Trpv1(-/-)mice 
		become substantially heavier than Trpv1(+/+) controls, thus 
		forming a paradoxical association between locomotor 
		hyperactivity and overweight. The present study solves this 
		contradiction. By using two experimental paradigms, we show that 
		aged Trpv1(-/-) mice have not an increased, but a decreased, 
		locomotor activity, as compared to age-matched Trpv1(+/+) 
		controls. We also confirm that aged Trpv1(-/-) mice are 
		overweight. We conclude that TRPV1 channels are involved in the 
		regulation of both general locomotor activity and body mass in 
		an age-dependent manner.},
	year = {2011},
	eissn = {1945-4589},
	pages = {450-454},
	orcid-numbers = {Garami, András/0000-0003-2493-0571}
}

@article{MTMT:1437739,
	title = {Contributions of different modes of TRPV1 activation to TRPV1 antagonist-induced hyperthermia.},
	url = {https://m2.mtmt.hu/api/publication/1437739},
	author = {Garami, András and Shimansky, YP and Pákai, Eszter and Oliveira, DL and Gavva, NR and Romanovsky, AA},
	doi = {10.1523/JNEUROSCI.5150-09.2010},
	journal-iso = {J NEUROSCI},
	journal = {JOURNAL OF NEUROSCIENCE},
	volume = {30},
	unique-id = {1437739},
	issn = {0270-6474},
	abstract = {Transient receptor potential vanilloid-1 (TRPV1) antagonists are widely viewed as next-generation pain therapeutics. However, these compounds cause hyperthermia, a serious side effect. TRPV1 antagonists differentially block three modes of TRPV1 activation: by heat, protons, and chemical ligands (e.g., capsaicin). We asked what combination of potencies in these three modes of TRPV1 activation corresponds to the lowest potency of a TRPV1 antagonist to cause hyperthermia. We studied hyperthermic responses of rats, mice, and guinea pigs to eight TRPV1 antagonists with different pharmacological profiles and used mathematical modeling to find a relative contribution of the blockade of each activation mode to the development of hyperthermia. We found that the hyperthermic effect has the highest sensitivity to the extent of TRPV1 blockade in the proton mode (0.43 to 0.65) with no to moderate sensitivity in the capsaicin mode (-0.01 to 0.34) and no sensitivity in the heat mode (0.00 to 0.01). We conclude that hyperthermia-free TRPV1 antagonists do not block TRPV1 activation by protons, even if they are potent blockers of the heat mode, and that decreasing the potency to block the capsaicin mode may further decrease the potency to cause hyperthermia.},
	keywords = {Animals; Male; MICE; RATS; Guinea Pigs; computer simulation; Dose-Response Relationship, Drug; Rats, Wistar; Mice, Knockout; Drug Evaluation, Preclinical/methods; Sensory System Agents/pharmacology; TRPV Cation Channels/*antagonists & inhibitors/*metabolism; Protons/therapeutic use; Neuropharmacology/methods; Hot Temperature/adverse effects; Fever/*chemically induced/*metabolism/physiopathology; Central Nervous System/*drug effects/*metabolism/physiopathology; Capsaicin/antagonists & inhibitors},
	year = {2010},
	eissn = {1529-2401},
	pages = {1435-1440},
	orcid-numbers = {Garami, András/0000-0003-2493-0571}
}

@article{MTMT:1423389,
	title = {Fasting hypometabolism and refeeding hyperphagia in rats: Effects of capsaicin desensitization of the abdominal vagus.},
	url = {https://m2.mtmt.hu/api/publication/1423389},
	author = {Garami, András and Balaskó, Márta and Székely, Miklós and Varjú-Solymár, Margit and Pétervári, Erika},
	doi = {10.1016/j.ejphar.2010.07.002},
	journal-iso = {EUR J PHARMACOL},
	journal = {EUROPEAN JOURNAL OF PHARMACOLOGY},
	volume = {644},
	unique-id = {1423389},
	issn = {0014-2999},
	abstract = {Capsaicin-sensitive abdominal vagal fibers contribute to postprandial satiety and hypermetabolism. We hypothesized that the hypometabolic adaptation to fasting involves similar mechanisms and that blockade of such signals might enhance loss of body weight upon fasting. A low dosage of capsaicin (5mg/kg) administered intraperitoneally desensitizes the local afferent vagal nerve endings for approximately three weeks without causing systemic desensitization or damaging the efferent fibers. Following such desensitization, male Wistar rats deprived of food for 120h lost significantly (18.9 + or - 0.4% vs. 15.8 + or - 1.0%), i.e. 20% more weight than the controls. Based on the present results, this can only be explained by the demonstrated defective hypometabolic adaptation in desensitized animals. Other mechanisms do not seem to make up for this defective function. Upon refeeding following a period of fasting, in the first 0.5-3h the food intake was significantly greater in capsaicin pretreated compared to the control group, demonstrating blockade of satiety as a sign of desensitization. The delayed gastrointestinal passage supported that vagal afferent nerve endings were in a desensitized state in these rats. In conclusion, local desensitization of the abdominal capsaicin-sensitive fibers attenuates the hypometabolic adaptation to food deprivation and the lack of fasting-induced activation of these fibers cannot be substituted by other fasting-dependent mechanisms. It is suggested that reports of low body weight in mice lacking the transient receptor potential vanilloid-1 channel and in rats with systemic capsaicin desensitization might be explained by a lasting absence of similar (vagus-mediated) hypometabolic processes, preventing weight gain or obesity.},
	keywords = {Animals; Male; RATS; Time Factors; Rats, Wistar; Weight Gain/drug effects; Feeding Behavior/drug effects; Weight Loss/drug effects; Vagus Nerve/*drug effects/metabolism; Satiety Response/*drug effects; Hyperphagia/*etiology; Fasting/physiology; Capsaicin/*pharmacology},
	year = {2010},
	eissn = {1879-0712},
	pages = {61-66},
	orcid-numbers = {Garami, András/0000-0003-2493-0571; Varjú-Solymár, Margit/0000-0001-6667-6263; Pétervári, Erika/0000-0002-3673-8491}
}

@article{MTMT:1461684,
	title = {The transient receptor potential vanilloid-1 channel in thermoregulation: a thermosensor it is not.},
	url = {https://m2.mtmt.hu/api/publication/1461684},
	author = {Romanovsky, AA and Almeida, MC and Garami, András and Steiner, AA and Norman, MH and Morrison, SF and Nakamura, K and Burmeister, JJ and Nucci, TB},
	doi = {10.1124/pr.109.001263},
	journal-iso = {PHARMACOL REV},
	journal = {PHARMACOLOGICAL REVIEWS},
	volume = {61},
	unique-id = {1461684},
	issn = {0031-6997},
	abstract = {The development of antagonists of the transient receptor potential vanilloid-1 (TRPV1) channel as pain therapeutics has revealed that these compounds cause hyperthermia in humans. This undesirable on-target side effect has triggered a surge of interest in the role of TRPV1 in thermoregulation and revived the hypothesis that TRPV1 channels serve as thermosensors. We review literature data on the distribution of TRPV1 channels in the body and on thermoregulatory responses to TRPV1 agonists and antagonists. We propose that two principal populations of TRPV1-expressing cells have connections with efferent thermoeffector pathways: 1) first-order sensory (polymodal), glutamatergic dorsal-root (and possibly nodose) ganglia neurons that innervate the abdominal viscera and 2) higher-order sensory, glutamatergic neurons presumably located in the median preoptic hypothalamic nucleus. We further hypothesize that all thermoregulatory responses to TRPV1 agonists and antagonists and thermoregulatory manifestations of TRPV1 desensitization stem from primary actions on these two neuronal populations. Agonists act primarily centrally on population 2; antagonists act primarily peripherally on population 1. We analyze what roles TRPV1 might play in thermoregulation and conclude that this channel does not serve as a thermosensor, at least not under physiological conditions. In the hypothalamus, TRPV1 channels are inactive at common brain temperatures. In the abdomen, TRPV1 channels are tonically activated, but not by temperature. However, tonic activation of visceral TRPV1 by nonthermal factors suppresses autonomic cold-defense effectors and, consequently, body temperature. Blockade of this activation by TRPV1 antagonists disinhibits thermoeffectors and causes hyperthermia. Strategies for creating hyperthermia-free TRPV1 antagonists are outlined. The potential physiological and pathological significance of TRPV1-mediated thermoregulatory effects is discussed.},
	keywords = {Animals; Humans; Models, Biological; Body Temperature Regulation/*physiology; TRPV Cation Channels/agonists/antagonists & inhibitors/*physiology},
	year = {2009},
	eissn = {1521-0081},
	pages = {228-261},
	orcid-numbers = {Garami, András/0000-0003-2493-0571}
}