@article{MTMT:31325981,
	title = {Long-term systemic administration of kynurenic acid brain region specifically elevates the abundance of functional CB1 receptors in rats.},
	url = {https://m2.mtmt.hu/api/publication/31325981},
	author = {Zádor, Ferenc and Nagy-Grócz, Gábor and Dvorácskó, Szabolcs and Bohár, Zsuzsanna and Cseh, Edina Katalin and Zádori, Dénes and Párdutz, Árpád and Szűcs, Edina and Tömböly, Csaba and Borsodi, Anna and Benyhe, Sándor and Vécsei, László},
	doi = {10.1016/j.neuint.2020.104752},
	journal-iso = {NEUROCHEM INT},
	journal = {NEUROCHEMISTRY INTERNATIONAL},
	volume = {138},
	unique-id = {31325981},
	issn = {0197-0186},
	abstract = {Kynurenic acid (KYNA) is one of the most significant metabolite of the kynurenine pathway both in terms of functional and potential therapeutic value. It is an N-methyl-D-aspartate (NMDA) receptor antagonist, but it can also activate the G-protein coupled receptor 35 (GPR35), which shares several structural and functional properties with cannabinoid receptors. Previously our group demonstrated that systemic chronic KYNA treatment altered opioid receptor G-protein activity. Opioid receptors also overlap in many features with cannabinoid receptors. Thus, our aim was to examine the direct in vitro and systemic, chronic in vivo effect of KYNA on type 1 cannabinoid receptor (CB1R) binding and G-protein activity. Based on competition and [35S]GTPγS G-protein binding assays in rat brain, KYNA alone did not show significant binding towards the CB1R, nor did it alter CB1R ligand binding and agonist activity in vitro. When rats were chronically treated with KYNA (single daily, i.p., 128 mg/kg for 9 days), the KYNA plasma and cerebrospinal fluid levels significantly increased compared to vehicle treated group. Furthermore, in G-protein binding assays, in the whole brain the amount of G-proteins in basal and in maximum activity coupled to the CB1R also increased due to the treatment. At the same time, the overall stimulatory properties of the receptor remained unaltered in vehicle and KYNA treated samples. Similar observations were made in rat hippocampus, but not in the cortex and brainstem. In saturation binding assays the density of CB1Rs in rat whole brain and hippocampus were also significantly enhanced after the same treatment, without significantly affecting ligand binding affinity. Thus, KYNA indirectly and brain region specifically increases the abundance of functional CB1Rs, without modifying the overall binding and activity of the receptor. Supposedly, this can be a compensatory mechanism on the part of the endocannabinoid system induced by the long-term KYNA exposure.},
	keywords = {RADIOLIGAND BINDING; hippocampus; kynurenic acid; G-PROTEIN; type 1 cannabinoid receptor; [(35)S]GTPγS binding},
	year = {2020},
	eissn = {1872-9754},
	orcid-numbers = {Nagy-Grócz, Gábor/0000-0003-2121-4625; Zádori, Dénes/0000-0003-0749-7980; Vécsei, László/0000-0001-8037-3672}
}

@article{MTMT:3372674,
	title = {The effect of increased NaCl intake on rat brain endogenous μ-opioid receptor signalling},
	url = {https://m2.mtmt.hu/api/publication/3372674},
	author = {Dadam, F and Zádor, Ferenc and Caeiro, X and Szűcs, Edina and Erdei, Anna and Samavati, Reza and Gáspár, Róbert and Borsodi, Anna and Vivas, L},
	doi = {10.1111/jne.12585},
	journal-iso = {J NEUROENDOCRINOL},
	journal = {JOURNAL OF NEUROENDOCRINOLOGY},
	volume = {30},
	unique-id = {3372674},
	issn = {0953-8194},
	abstract = {Numerous studies demonstrate the significant role of central -endorphin and its receptor, the mu-opioid receptor (MOR), in sodium intake regulation. The present study aimed to investigate the possible relationship between chronic high-NaCl intake and brain endogenous MOR functioning. We examined whether short-term (4 days) obligatory salt intake (2% NaCl solution) in rats induces changes in MOR mRNA expression, G-protein activity and MOR binding capacity in brain regions involved in salt intake regulation. Plasma osmolality and electrolyte concentrations after sodium overload and the initial and final body weight of the animals were also examined. After 4 days of obligatory hypertonic sodium chloride intake, there was clearly no difference in MOR mRNA expression and G-protein activity in the median preoptic nucleus (MnPO). In the brainstem, MOR binding capacity also remained unaltered, although the maximal efficacy of MOR G-protein significantly increased. Finally, no significant alterations were observed in plasma osmolality and electrolyte concentrations. Interestingly, animals that received sodium gained significantly less weight than control animals. In conclusion, we found no significant alterations in the MnPO and brainstem in the number of available cell surface MORs or de novo syntheses of MOR after hypertonic sodium intake. The increased MOR G-protein activity following acute sodium overconsumption may participate in the maintenance of normal blood pressure levels and/or in enhancing sodium taste aversion and sodium overload-induced anorexia.},
	keywords = {ACTIVATION; GENE-EXPRESSION; SOLITARY TRACT; AGONIST; BETA-ENDORPHIN; brainstem; Appetite; salt intake; lateral parabrachial nucleus; HYPERTONIC SODIUM-INTAKE; sodium ingestion; G-protein activation; mu-opioid receptor signalling; amygdala},
	year = {2018},
	eissn = {1365-2826},
	orcid-numbers = {Gáspár, Róbert/0000-0002-1571-7579}
}

@article{MTMT:3213626,
	title = {Characterization of [3H] oxymorphone binding sites in mouse brain: Quantitative autoradiography in opioid receptor knockout mice},
	url = {https://m2.mtmt.hu/api/publication/3213626},
	author = {Yoo, JH and Borsodi, Anna and Tóth, Géza and Benyhe, Sándor and Gáspár, Róbert and Matifas, A and Kieffer, BL and Metaxas, A and Kitchen, I and Bailey, A},
	doi = {10.1016/j.neulet.2017.02.002},
	journal-iso = {NEUROSCI LETT},
	journal = {NEUROSCIENCE LETTERS},
	volume = {643},
	unique-id = {3213626},
	issn = {0304-3940},
	abstract = {Oxymorphone, one of oxycodone's metabolic products, is a potent opioid receptor agonist which is thought to contribute to the analgesic effect of its parent compound and may have high potential abuse liability. Nonetheless, the in vivo pharmacological binding profile of this drug is still unclear. This study uses mice lacking mu (MOP), kappa (KOP) or delta (DOP) opioid receptors as well as mice lacking all three opioid receptors to provide full characterisation of oxymorphone binding sites in the brain. Saturation binding studies using [H-3]oxymorphone revealed high affinity binding sites in mouse brain displaying Kd of 1.7 nM and Bmax of 147 fmol/mg. Furthermore, we performed quantitative autoradiography binding studies using [H-3]oxymorphone in mouse brain. The distribution of [H-3]oxymorphone binding sites was found to be similar to the selective MOP agonist [H-3]DAMGO in the mouse brain. [H-3]Oxymorphone binding was completely abolished across the majority of the brain regions in mice lacking MOP as well as in mice lacking all three opioid receptors. DOP and KOP knockout mice retained [H-3]oxymorphone binding sites suggesting oxymorphone may not target DOP or KOP. These results confirm that the MOP, and not the DOP or the KOP is the main high affinity binding target for oxymorphone. (C) 2017 Elsevier B.V. All rights reserved.},
	keywords = {GENE; ACTIVATION; AUTORADIOGRAPHY; MOUSE; MU; Dimerization; Knockout; WITHDRAWAL; ABUSE; Extended-release; oxycodone; Opioid; BACK-PAIN; DOPAMINE TRANSPORTER BINDING; [H-3]Oxymorphone},
	year = {2017},
	eissn = {1872-7972},
	pages = {16-21},
	orcid-numbers = {Gáspár, Róbert/0000-0002-1571-7579}
}

@article{MTMT:3198611,
	title = {Kynurenic acid and its analogue can alter the opioid receptor G-protein signaling after acute treatment via NMDA receptor in rat cortex and striatum},
	url = {https://m2.mtmt.hu/api/publication/3198611},
	author = {Samavati, Reza and Zádor, Ferenc and Szűcs, Edina and Tuka, Bernadett and Martos, Diána and Veres, Gábor and Gáspár, Róbert and Mándity, István and Fülöp, Ferenc and Vécsei, László and Benyhe, Sándor and Borsodi, Anna},
	doi = {10.1016/j.jns.2017.02.053},
	journal-iso = {J NEUROL SCI},
	journal = {JOURNAL OF THE NEUROLOGICAL SCIENCES},
	volume = {376},
	unique-id = {3198611},
	issn = {0022-510X},
	keywords = {OPIOID RECEPTOR; MK-801; G-PROTEIN; KYNA; [35S]GTPγS binding},
	year = {2017},
	eissn = {1878-5883},
	pages = {63-70},
	orcid-numbers = {Tuka, Bernadett/0000-0002-1410-4666; Gáspár, Róbert/0000-0002-1571-7579; Mándity, István/0000-0003-2865-6143; Fülöp, Ferenc/0000-0003-1066-5287; Vécsei, László/0000-0001-8037-3672}
}

@article{MTMT:3157890,
	title = {A NOVEL NON-OPIOID BINDING SITE FOR ENDOMORPHIN-1},
	url = {https://m2.mtmt.hu/api/publication/3157890},
	author = {Lengyel, Imre and Tóth, Fanni and Biyashev, Daureen and Szatmári, Ildikó and Monory, K and Tömböly, Csaba and Tóth, Géza and Benyhe, Sándor and Borsodi, Anna},
	journal-iso = {J PHYSIOL PHARMACOL},
	journal = {JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY},
	volume = {67},
	unique-id = {3157890},
	issn = {0867-5910},
	abstract = {Endomorphins are natural amidated opioid tetrapeptides with the following structure: Tyr-Pro-Trp-Phe-NH2 (endomorphin-1), and Tyr-Pro-Phe-Phe-NH2 (endomorphin-2). Endomorphins interact selectively with the mu-opioid or MOP receptors and exhibit nanomolar or sub-nanomolar receptor binding affinities, therefore they suggested to be endogenous agonists for the mu-pioid receptors. Endomorphins mediate a number of characteristic opioid effects, such as antinociception, however there are several physiological functions in which endomorphins appear to act in a fashion that does not involve binding to and activation of the mu-opioid receptor. Our recent data indicate that a radiolabelled [H-3]endomorphin-1 with a specific radioactivity of 2.35 TBq/mmol -prepared by catalytic dehalogenation of the diiodinated peptide precursor in the presence of tritium gas-is able to bind to a second, naloxone insensitive recognition site in rat brain membranes. Binding heterogeneity, i.e., the presence of higher (K-d = 0.4 nM /B-max = 120 fmol/mg protein) and lower (K-d = 8.2 nM /B-max,, = 432 fmol/mg protein) affinity binding components is observed both in saturation binding experiments followed by Schatchard analysis, and in equilibrium competition binding studies. The signs of receptor multiplicity, e.g., curvilinear Schatchard plots or biphasic displacement curves are seen only if the nonspecific binding is measured in the presence of excess unlabeled endomorphin-1 and not in the presence of excess unlabeled naloxone. The second, lower affinity non-opioid binding site is not recognized by heterocyclic opioid alkaloid ligands, neither agonists such as morphine, nor antagonists such as naloxone. On the contrary, endomorphin-1 is displaced from its lower affinity, higher capacity binding site by several natural neuropeptides, including methionine-enkephalin-Arg-Phe, nociceptin-orphanin FQ, angiotensin and FMRF-amide. This naloxone-insensitive, consequently non-opioid binding site seems to be present in nervous tissues carrying low density or no mu-opioid receptors, such as rodent cerebellum, or brain of mu-opioid receptor deficient (MOPr-/-) transgenic or 'knock-out' (K.O.) mice. The newly described non-opioid binding component is not coupled to regulatory G-proteins, nor does it affect adenylyl cyclase enzyme activity. Taken together endomorphin-1 carries opioid and, in addition to non-opioid functions that needs to be taken into account when various effects of endomorphin-1 are evaluated in physiological or pathologic conditions.},
	keywords = {CELLS; RAT-BRAIN; ADENYLYL-CYCLASE; AGONIST; RADIOLIGAND BINDING; MORPHINE; OPIATE RECEPTOR; DELTA; Rat brain; MU-OPIOID-RECEPTOR; KNOCK-OUT MICE; Tritiated endomorphin-1; Naloxone insensitive site; AFFINITY STATES; mu-opioid peptide receptor; G-protein activation},
	year = {2016},
	eissn = {1899-1505},
	pages = {605-616},
	orcid-numbers = {Szatmári, Ildikó/0000-0003-1040-145X}
}

@article{MTMT:3081476,
	title = {The effects of progesterone on the alpha2-adrenergic receptor subtypes in late-pregnant uterine contractions in vitro},
	url = {https://m2.mtmt.hu/api/publication/3081476},
	author = {Hajagos-Tóth, Judit and Bóta, Judit and Ducza, Eszter and Samavati, Reza and Borsodi, Anna and Benyhe, Sándor and Gáspár, Róbert},
	doi = {10.1186/s12958-016-0166-9},
	journal-iso = {REPROD BIOL ENDOCRIN},
	journal = {REPRODUCTIVE BIOLOGY AND ENDOCRINOLOGY},
	volume = {14},
	unique-id = {3081476},
	issn = {1477-7827},
	year = {2016},
	eissn = {1477-7827},
	orcid-numbers = {Gáspár, Róbert/0000-0002-1571-7579}
}

@article{MTMT:3049250,
	title = {The effects of estrogen on the α2-adrenergic receptor subtypes in rat uterine function in late pregnancy in vitro},
	url = {https://m2.mtmt.hu/api/publication/3049250},
	author = {Hajagos-Tóth, Judit and Bóta, Judit and Ducza, Eszter and Csányi, Adrienn and Tiszai, Zita and Borsodi, Anna and Samavati, Reza and Benyhe, Sándor and Gáspár, Róbert},
	doi = {10.3325/cmj.2016.57.100},
	journal-iso = {CROAT MED J},
	journal = {CROATIAN MEDICAL JOURNAL},
	volume = {57},
	unique-id = {3049250},
	issn = {0353-9504},
	year = {2016},
	eissn = {1332-8166},
	pages = {100-109},
	orcid-numbers = {Csányi, Adrienn/0000-0001-6905-6334; Gáspár, Róbert/0000-0002-1571-7579}
}

@article{MTMT:2989937,
	title = {The effects of female sexual hormones on the expression and function of α1A- and α1D-adrenoceptor subtypes in the late-pregnant rat myometrium},
	url = {https://m2.mtmt.hu/api/publication/2989937},
	author = {Bóta, Judit and Hajagos-Tóth, Judit and Ducza, Eszter and Samavati, Reza and Borsodi, Anna and Benyhe, Sándor and Gáspár, Róbert},
	doi = {10.1016/j.ejphar.2015.11.015},
	journal-iso = {EUR J PHARMACOL},
	journal = {EUROPEAN JOURNAL OF PHARMACOLOGY},
	volume = {769},
	unique-id = {2989937},
	issn = {0014-2999},
	abstract = {The aim of the study was to investigate the roles of α1-adrenoceptor subtypes in the last-day pregnant rat uterus in vitro by the administration of subtype-specific antagonists (the α1A-adrenoceptor antagonist WB 4101 and the α1D-adrenoceptor antagonist BMY 7378) after 17β-estradiol or progesterone pretreatment. In isolated organ bath studies, contractions were elicited with (-)-noradrenaline (10-8-10-5 M) in the presence of propranolol (10-5 M) and yohimbine (10-6 M) in order to avoid β-, and α2-adrenergic action. The myometrial expressions of the α1-adrenoceptor subtypes were determined by means of the real time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting techniques. The activated G protein levels were investigated through radiolabelled GTP binding assays. Both 17β-estradiol and progesterone pretreatment changed the myometrial contracting effect of (-)-noradrenaline. In the presence of WB 4101, progesterone pretreatment decreased the (-)-noradrenaline-induced myometrial contraction. In the presence of BMY 7378, both the 17β-estradiol and the progesterone pretreatment reduced the effect of (-)-noradrenaline. The mRNA and protein expressions of the α1A-adrenoceptors were decreased after 17β-estradiol pretreatment. (-)-Noradrenaline increased the [35S]GTPγS binding of the α1-adrenoceptors, which was most markedly elevated by progesterone. Pertussis toxin inhibited the [35S]GTPγS binding-stimulating effect of (-)-noradrenaline, indicating the role of Gi proteins in the signal mechanisms. 17β-estradiol pretreatment blocks the expression of the α1A-adrenoceptors, whereas it does not influence the expression of the α1D-adrenoceptors. Progesterone pretreatment does not have any effect on the myometrial mRNA and protein expressions of the α1-adrenoceptors, but it alters the G protein coupling of these receptors, promoting a Gi-dependent pathway. © 2015 Elsevier B.V. All rights reserved.},
	keywords = {Female; Male; ARTICLE; signal transduction; ESTRADIOL; protein analysis; priority journal; controlled study; nonhuman; animal tissue; animal experiment; in vitro study; pregnancy; PROGESTERONE; PROTEIN FUNCTION; protein expression; messenger rna; PROPRANOLOL; yohimbine; uterus contraction; pertussis toxin; guanosine 5' o (3 thiotriphosphate); 17β-estradiol; inhibitory guanine nucleotide binding protein; alpha 1A adrenergic receptor; GTPgammaS binding assay; alpha 1D adrenergic receptor; 8 [2 [4 (2 methoxyphenyl) 1 piperazinyl]ethyl] 8 azaspiro[4.5]decane 7,9 dione; 2 [[2 (2,6 dimethoxyphenoxy)ethyl]aminomethyl] 1,4 benzodioxan; α1-adrenoreceptor subtypes; Myometrial contractility; rat},
	year = {2015},
	eissn = {1879-0712},
	pages = {177-184},
	orcid-numbers = {Gáspár, Róbert/0000-0002-1571-7579}
}

@article{MTMT:2964613,
	title = {Further Characterization of Hemopressin Peptide Fragments in the Opioid and Cannabinoid Systems},
	url = {https://m2.mtmt.hu/api/publication/2964613},
	author = {Szlávicz, Eszter and Perera, PS and Tömböly, Csaba and Helyes, Zsuzsanna and Zádor, Ferenc and Benyhe, Sándor and Borsodi, Anna and Bojnik, Engin},
	doi = {10.1213/ANE.0000000000000964},
	journal-iso = {ANESTH ANALG},
	journal = {ANESTHESIA AND ANALGESIA},
	volume = {121},
	unique-id = {2964613},
	issn = {0003-2999},
	abstract = {BACKGROUND:: Hemopressin, so-called because of its hypotensive effect, belongs to the derivatives of the hemoglobin α-chain. It was isolated from rat brain membrane homogenate by the use of catalytically inactive forms of endopeptidase 24.15 and neurolysin. Hemopressin has antihyperalgesic features that cannot be prevented by the opioid receptor antagonist, naloxone. METHODS:: In the present study, we investigated whether hemopressin (PVNFKFLSH) and its C-terminally truncated fragment hemopressin 1–7 (PVNFKFL) have any influence on opioid-dependent signaling. Peptides have been analyzed using G-protein–stimulating functional and receptor bindings in this experimental setup. RESULTS:: These 2 compounds efficiently activated the G-proteins, and naloxone slightly blocked this stimulation. At the same time, they were able to displace radiolabeled [H]DAMGO, a selective ligand for μ-opioid system, at micromolar concentrations. Displacement caused by the heptapeptide was more modest compared with hemopressin. Experiments performed on cell lines overexpressing μ-opioid receptors verified the opioid activity of both hemopressins. Moreover, the CB1 cannabinoid receptor antagonist, AM251, significantly decreased their G-protein stimulatory effect. CONCLUSIONS:: Here, we further confirm that hemopressins can modulate CB1 receptors and can have a slight modulatory effect on the opioid system. © 2015 International Anesthesia Research Society.},
	year = {2015},
	eissn = {1526-7598},
	pages = {1488-1494},
	orcid-numbers = {Szlávicz, Eszter/0000-0002-1083-0994}
}

@article{MTMT:2796553,
	title = {Design, Synthesis and Biological Evaluation of Two Opioid Agonist and Ca 2.2 Blocker Multitarget Ligands.},
	url = {https://m2.mtmt.hu/api/publication/2796553},
	author = {Mollica, A and Costante, R and Novellino, E and Stefanucci, A and Pieretti, S and Zádor, Ferenc and Samavati, Reza and Borsodi, Anna and Benyhe, Sándor and Vetter, I and Lewis, RJ},
	doi = {10.1111/cbdd.12479},
	journal-iso = {CHEM BIOL DRUG DES},
	journal = {CHEMICAL BIOLOGY & DRUG DESIGN},
	volume = {86},
	unique-id = {2796553},
	issn = {1747-0277},
	abstract = {N-type voltage-dependent Ca2+ channels (CaV 2.2) are located at nerve endings in the central and peripheral nervous systems and are strongly associated with the pathological processes of cerebral ischaemia and neuropathic pain. CaV 2.2 blockers such as the omega-conotoxin MVIIA (Prialt) are analgesic and have opioid-sparing effects. With the aim to develop new multitarget analgesic compounds, we designed the first omega-conotoxin/opioid peptidomimetics based on the enkephalin-like sequence Tyr-D-Ala-Gly-Phe (for the opioid portion) and two fragments derived from the loop-2 pharmacophore of omega-conotoxin MVIIA. Antinociceptive activity evaluated in vitro and in vivo revealed differential affinity for CaV 2.2 and opioid receptors and no significant synergistic activity.},
	year = {2015},
	eissn = {1747-0285},
	pages = {156-162}
}