TY - JOUR AU - Vas, Szilvia AU - Papp, Rege Sugárka AU - Könczöl, Katalin AU - Bogáthy, Emese AU - Papp, Noémi AU - Ádori, Csaba AU - Durst, Máté AU - Sípos, Klaudia AU - Ocskay, Klementina AU - Farkas, Imre AU - Bálint, Flóra AU - Ferenczi, Szilamér AU - Török, Bibiána AU - Kovács, Anita AU - Szabó, Evelin AU - Zelena, Dóra AU - Kovács, Krisztina AU - Földes, Anna AU - Kató, Erzsébet AU - Köles, László AU - Bagdy, György AU - Palkovits, Miklós AU - Tóth, Zsuzsanna TI - Prolactin-releasing peptide contributes to stress-related mood disorders and inhibits sleep/mood regulatory melanin-concentrating hormone neurons in rats. JF - JOURNAL OF NEUROSCIENCE J2 - J NEUROSCI VL - 43 PY - 2023 IS - 5 SP - 846 EP - 862 PG - 17 SN - 0270-6474 DO - 10.1523/JNEUROSCI.2139-21.2022 UR - https://m2.mtmt.hu/api/publication/33543493 ID - 33543493 AB - Stress disorders impair sleep, quality of life, however, their pathomechanisms are unknown. Prolactin-releasing peptide (PrRP) is a stress mediator, therefore, we hypothesised that PrRP may be involved in the development of stress disorders. PrRP is produced by the medullary A1/A2 noradrenaline (NA) cells, which transmit stress signals to forebrain centers, and by non-NA cells in the hypothalamic dorsomedial nucleus. We found in male rats that both PrRP and PrRP-NA cells innervate melanin-concentrating hormone (MCH) producing neurons in the dorsolateral hypothalamus (DLH). These cells serve as a key hub for regulating sleep and affective states. Ex vivo, PrRP hyperpolarized MCH neurons and further increased the hyperpolarization caused by NA. Following sleep deprivation, intracerebroventricular PrRP injection reduced the number of REM sleep-active MCH cells. PrRP expression in the dorsomedial nucleus was up-regulated by sleep deprivation, while down-regulated by REM sleep rebound. Both in learned helplessness paradigm and after peripheral inflammation, impaired coping with sustained stress was associated with (i) overactivation of PrRP cells, (ii) PrRP protein and receptor depletion in the DLH, and (iii) dysregulation of MCH expression. Exposure to stress in PrRP insensitive period led to increased passive coping with stress. Normal PrRP signaling, therefore, seems to protect animals against stress-related disorders. PrRP signaling in the DLH is important component of the PrRP's action, which may be mediated by MCH neurons. Moreover, PrRP receptors were downregulated in the DLH of human suicidal victims. As stress-related mental disorders are the leading cause of suicide, our findings may have particular translational relevance.SIGNIFICANCE STATEMENT:Treatment resistance to monoaminergic antidepressants is a major problem. Neuropeptides that modulate the central monoaminergic signaling are promising targets for developing alternative therapeutic strategies. We found that stress-responsive prolactin-releasing peptide (PrRP) cells innervated melanin-concentrating hormone (MCH) neurons that are crucial in the regulation of sleep and mood. PrRP inhibited MCH cell activity and enhanced the inhibitory effect evoked by noradrenaline, a classic monoamine, on MCH neurons. We observed that impaired PrRP signaling led to failure in coping with chronic/repeated stress and was associated with altered MCH expression. We found alterations of the PrRP system also in suicidal human subjects. PrRP dysfunction may underlie stress disorders, and fine-tuning MCH activity by PrRP may be an important part of the mechanism. LA - English DB - MTMT ER - TY - JOUR AU - Köles, László AU - Riba, Pál AU - Al-Khrasani, Mahmoud AU - Brenner, Gábor AU - Giricz, Zoltán AU - Görbe, Anikó AU - Kató, Erzsébet AU - Király, Kornél P AU - Miklya, Ildikó AU - Varga, Zoltán AU - Zádori, Zoltán Sándor AU - Ferdinandy, Péter TI - Digitális távoktatás a COVID-19-járvány árnyékában – összhangban az orvosképzés megújulásával és modernizálásával a Semmelweis Egyetem Farmakológiai és Farmakoterápiás Intézetében JF - ORVOSKÉPZÉS J2 - ORVOSKÉPZÉS VL - 96 PY - 2021 IS - 2 SP - 261 EP - 264 PG - 4 SN - 0030-6037 UR - https://m2.mtmt.hu/api/publication/34139029 ID - 34139029 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Kádár, Kristóf György AU - Juhász, Viktória Orsolya AU - Földes, Anna AU - Rácz, Róbert AU - Zhang, Y. AU - Löchli, H. AU - Kató, Erzsébet AU - Köles, László AU - Steward, Martin Charles AU - Denbesten, P. AU - Varga, Gábor AU - Zsembery, Ákos TI - Trpm7-mediated calcium transport in hat-7 ameloblasts JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 22 PY - 2021 IS - 8 PG - 14 SN - 1661-6596 DO - 10.3390/ijms22083992 UR - https://m2.mtmt.hu/api/publication/31981561 ID - 31981561 N1 - Összes idézések száma a WoS-ban: 0 AB - TRPM7 plays an important role in cellular Ca2+, Zn2+ and Mg2+ homeostasis. TRPM7 channels are abundantly expressed in ameloblasts and, in the absence of TRPM7, dental enamel is hypomineralized. The potential role of TRPM7 channels in Ca2+ transport during amelogenesis was investigated in the HAT-7 rat ameloblast cell line. The cells showed strong TRPM7 mRNA and protein expression. Characteristic TRPM7 transmembrane currents were observed, which increased in the absence of intracellular Mg2+ ([Mg2+]i ), were reduced by elevated [Mg2+]i, and were inhibited by the TRPM7 inhibitors NS8593 and FTY720. Mibefradil evoked similar currents, which were suppressed by elevated [Mg2+]i, reducing extracellular pH stimulated transmembrane currents, which were inhibited by FTY720. Naltriben and mibefradil both evoked Ca2+ influx, which was further enhanced by the acidic intracellular conditions. The SOCE inhibitor BTP2 blocked Ca2+ entry induced by naltriben but not by mibefradil. Thus, in HAT-7 cells, TRPM7 may serves both as a potential modulator of Orai-dependent Ca2+ uptake and as an independent Ca2+ entry pathway sensitive to pH. Therefore, TRPM7 may contribute directly to transepithelial Ca2+ transport in amelogenesis. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. LA - English DB - MTMT ER - TY - CHAP AU - Szalka, András AU - Kató, Erzsébet ED - Gyires, Klára ED - Fürst, Zsuzsanna ED - Ferdinandy, Péter ED - Pintér, Erika ED - Szilvássy, Zoltán ED - Varró, András TI - Féreg- és rovarellenes szerek T2 - Farmakológia és klinikai farmakológia PB - Medicina Könyvkiadó CY - Budapest SN - 9782632267388 PY - 2020 SP - 848 EP - 853 PG - 6 UR - https://m2.mtmt.hu/api/publication/31611024 ID - 31611024 LA - Hungarian DB - MTMT ER - TY - CHAP AU - Szalka, András AU - Kató, Erzsébet ED - Gyires, Klára ED - Fürst, Zsuzsanna ED - Ferdinandy, Péter ED - Pintér, Erika ED - Szilvássy, Zoltán ED - Varró, András TI - Protozoonellenes szerek T2 - Farmakológia és klinikai farmakológia PB - Medicina Könyvkiadó CY - Budapest SN - 9782632267388 PY - 2020 SP - 839 EP - 847 PG - 9 UR - https://m2.mtmt.hu/api/publication/31611021 ID - 31611021 LA - Hungarian DB - MTMT ER - TY - CHAP AU - Köles, László AU - Kató, Erzsébet ED - Gyires, Klára ED - Fürst, Zsuzsanna ED - Ferdinandy, Péter ED - Pintér, Erika ED - Szilvássy, Zoltán ED - Varró, András TI - A véralvadást befolyásoló szerek T2 - Farmakológia és klinikai farmakológia PB - Medicina Könyvkiadó CY - Budapest SN - 9782632267388 PY - 2020 SP - 545 EP - 559 PG - 15 UR - https://m2.mtmt.hu/api/publication/31610813 ID - 31610813 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Koványi, Bence AU - Csölle, Cecília AU - Calovi, Stefano AU - Hanuska, Adrienn AU - Kató, Erzsébet AU - Köles, László AU - Bhattacharya, A AU - Haller, József AU - Sperlágh, Beáta TI - The role of P2X7 receptors in a rodent PCP-induced schizophrenia model JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 6 PY - 2016 PG - 16 SN - 2045-2322 DO - 10.1038/srep36680 UR - https://m2.mtmt.hu/api/publication/3143505 ID - 3143505 N1 - Laboratory of Molecular Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences (IEM HAS), Budapest, H-1450, Hungary János Szentágothai School of Neurosciences, Semmelweis University School of PhD Studies, Budapest, Hungary Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Budapest, H-1089, Hungary Janssen Research and Development, LLC, Neuroscience TA, San Diego, CA 92121, United States Department of Behavioral Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences (IEM HAS), Budapest, H-1450, Hungary Gedeon Richter Plc., Budapest, Hungary Cited By :29 Export Date: 13 May 2022 Correspondence Address: Sperlágh, B.; Laboratory of Molecular Pharmacology, Hungary; email: sperlagh@koki.hu Chemicals/CAS: nicotinamide, 11032-50-1, 98-92-0; phencyclidine, 77-10-1, 956-90-1; JNJ-47965567; Niacinamide; Phencyclidine; Piperazines; Purinergic P2X Receptor Antagonists; Receptors, Purinergic P2X7 Funding details: KTIA-13-NAP-A-III/1to B.S. Funding details: 101645, 116654, NN107234 Funding details: Seventh Framework Programme, FP7, 294313 Funding details: European Research Council, ERC Funding text 1: This study was supported by research grants from the Hungarian Research and Development Fund (Grant NN107234 and 116654 to B.S.; Grant 101645 to J.H.), the European Research Council (Grant 294313-SERRACO to B.S.), and the Hungarian Brain Research Program [KTIA-13-NAP-A-III/1to B.S.]. AB - P2X7 receptors (P2X7Rs) are ligand-gated ion channels sensitive to extracellular ATP. Here we examined for the first time the role of P2X7R in an animal model of schizophrenia. Using the PCP induced schizophrenia model we show that both genetic deletion and pharmacological inhibition of P2X7Rs alleviate schizophrenia-like behavioral alterations. In P2rx7+/+ mice, PCP induced hyperlocomotion, stereotype behavior, ataxia and social withdrawal. In P2X7 receptor deficient mice (P2rx7-/-), the social interactions were increased, whereas the PCP induced hyperlocomotion and stereotype behavior were alleviated. The selective P2X7 receptor antagonist JNJ-47965567 partly replicated the effect of gene deficiency on PCP-induced behavioral changes and counteracted PCP-induced social withdrawal. We also show that PCP treatment upregulates and increases the functional responsiveness of P2X7Rs in the prefrontal cortex of young adult animals. The amplitude of NMDA evoked currents recorded from layer V pyramidal neurons of cortical slices were slightly decreased by both genetic deletion of P2rx7 and by JNJ-47965567. PCP induced alterations in mRNA expression encoding schizophrenia-related genes, such as NR2A, NR2B, neuregulin 1, NR1 and GABA alpha1 subunit were absent in the PFC of young adult P2rx7-/- animals. Our findings point to P2X7R as a potential therapeutic target in schizophrenia. LA - English DB - MTMT ER - TY - JOUR AU - Köles, László AU - Kató, Erzsébet AU - Hanuska, Adrienn AU - Zádori, Zoltán Sándor AU - Al-Khrasani, Mahmoud AU - Zelles, Tibor AU - Rubini, P AU - Illes, P TI - Modulation of excitatory neurotransmission by neuronal/glial signalling molecules: interplay between purinergic and glutamatergic systems JF - PURINERGIC SIGNALLING J2 - PURINERG SIGNAL VL - 12 PY - 2016 IS - 1 SP - 1 EP - 24 PG - 24 SN - 1573-9538 DO - 10.1007/s11302-015-9480-5 UR - https://m2.mtmt.hu/api/publication/2981932 ID - 2981932 N1 - Department of Pharmacology and Pharmacotherapy, Semmelweis University, Nagyvárad tér 4, Budapest, 1089, Hungary Rudolf-Boehm-Institute of Pharmacology and Toxicology, University of Leipzig, Leipzig, 04107, Germany Cited By :31 Export Date: 7 September 2021 Correspondence Address: Köles, L.; Department of Pharmacology and Pharmacotherapy, Nagyvárad tér 4, Hungary; email: koles.laszlo@med.semmelweis-univ.hu Chemicals/CAS: acetylcholine, 51-84-3, 60-31-1, 66-23-9; amantadine, 665-66-7, 768-94-5; brain derived neurotrophic factor, 218441-99-7; cyclic AMP responsive element binding protein, 130428-87-4, 130939-96-7; dizocilpine, 77086-21-6; dopamine, 51-61-6, 62-31-7; ifenprodil, 23210-56-2; ketamine, 1867-66-9, 6740-88-1, 81771-21-3; memantine, 19982-08-2, 41100-52-1, 51052-62-1; mitogen activated protein kinase, 142243-02-5; phencyclidine, 77-10-1, 956-90-1; pregnenolone, 145-13-1; Receptors, AMPA; Receptors, Glutamate; Receptors, N-Methyl-D-Aspartate; Receptors, Purinergic LA - English DB - MTMT ER - TY - JOUR AU - Király, Kornél P AU - Caputi, FF AU - Hanuska, Adrienn AU - Kató, Erzsébet AU - Balogh, Mihály AU - Köles, László AU - Palmisano, M AU - Riba, Pál AU - Hosztafi, Sándor AU - Romualdi, P AU - Candeletti, S AU - Ferdinandy, Péter AU - Fürst, Zsuzsanna AU - Al-Khrasani, Mahmoud TI - A new potent analgesic agent with reduced liability to produce morphine tolerance JF - BRAIN RESEARCH BULLETIN J2 - BRAIN RES BULL VL - 117 PY - 2015 SP - 32 EP - 38 PG - 7 SN - 0361-9230 DO - 10.1016/j.brainresbull.2015.07.005 UR - https://m2.mtmt.hu/api/publication/2951337 ID - 2951337 N1 - Kiraly K and Caputi FF equally contributed to the work AB - The therapeutic use of opioids is limited by the development of tolerance to the analgesic effect and the cellular and molecular mechanisms underlying this phenomenon are still not completely understood. For this reason the search for new analgesic derivatives, endowed with lower tolerance, is always an active field. The newly synthesized 14-. O-Methylmorphine-6-sulfate (14-. O-MeM6SU) shows high efficacy in in vitro assays and a strong analgesic action in the rat tail flick test. The aim of present work was to investigate: the analgesic effect of 14-. O-MeM6SU in mouse tail-flick test; the tolerance to analgesic effect of 14-. O-MeM6SU compared to morphine in mice, the effects of test compounds on glutamatergic neurotransmission by measuring spontaneous excitatory postsynaptic currents (sEPSCs) of layer V pyramidal cells from rat prefrontal cortices; and the effect of acute and chronic 14-. O-MeM6SU treatments on opioid receptor gene expression in SH-SY5Y neuroblastoma cells expressing μ-opioid (MOP) and nociceptin/opioid receptor-like 1 (NOP) receptors.14-O-MeM6SU was 17 times more potent than morphine in analgesia and had long duration of action in analgesic dose equipotent to morphine. Mice were treated subcutaneously (s.c.) either with 200μmol/kg morphine or with 14-O-MeM6SU (12μmol/kg) twice daily for three days. The magnitude of tolerance or cross-tolerance indicated by the shift in antinociceptive ED50 measured was greater for morphine compared to 14-O-MeM6SU. Subsequent to behavioral testing, patch-clamp experiments in layer V pyramidal neurons of rat prefrontal cortical slices in the presence of bicuculline were performed. Both 14-O-MeM6SU (0.1μM) and morphine (1μM) decreased the frequency of sEPSCs, indicating reduction of glutamate release. The effect of the novel compound was reversed by the opioid receptor antagonist naloxone, indicating an opioid mediated action. In contrast, the amplitude was not affected. Finally, gene expression data showed a dose dependent down-regulation of MOP receptor after 24h and 48h exposure to 14-O-MeM6SU. Interestingly, no changes were detected for NOP receptor gene expression. The specific lack of this effect could be related to the lower tolerance development to analgesic effect of 14-O-MeM6SU. Furthermore, 14-O-MeM6SU displayed high intrinsic efficacy possibly an important factor in the observed effects. Further, the observed inhibition of glutamatergic signaling might be attributed also to the reduction of opioid tolerance. Based on our results the development of a new clinically important, safe analgesic agent might be possible. © 2015 Elsevier Inc. LA - English DB - MTMT ER - TY - JOUR AU - Ficker, C AU - Kovács-Rozmer, Katalin AU - Kató, Erzsébet AU - Andó, Rómeó AU - Schumann, L AU - Krügel, U AU - Franke, H AU - Sperlágh, Beáta AU - Riedel, T AU - Illes, P TI - Astrocyte-neuron interaction in the substantia gelatinosa of the spinal cord dorsal horn via P2X7 receptor-mediated release of glutamate and reactive oxygen species. JF - GLIA J2 - GLIA VL - 62 PY - 2014 IS - 10 SP - 1671 EP - 1686 PG - 16 SN - 0894-1491 DO - 10.1002/glia.22707 UR - https://m2.mtmt.hu/api/publication/2603498 ID - 2603498 N1 - Rudolf Boehm Institute for Pharmacology und Toxicology, University of Leipzig, Leipzig, Germany Department of Pharmacology and Pharmacotherapy, Semmelweis University, Hungary Laboratory of Molecular Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Hungary Cited By :42 Export Date: 7 March 2023 CODEN: GLIAE Correspondence Address: Illes, P.; Rudolf-Boehm-Institute for Pharmacology and Toxicology, Haertelstrasse 16-18, Leipzig, Germany; email: Peter.Illes@medizin.uni-leipzig.de Chemicals/CAS: 2 amino 5 phosphonovaleric acid, 76726-92-6; 3 [[5 (2,3 dichlorophenyl) 1h tetrazol 1 yl]methyl]pyridine, 899507-36-9; 6 cyano 7 nitro 2,3 quinoxalinedione, 115066-14-3; alpha amino 3 hydroxy 5 methyl 4 isoxazolepropionic acid, 77521-29-0; glutamic acid, 11070-68-1, 138-15-8, 56-86-0, 6899-05-4; muscimol, 2763-96-4; n methyl dextro aspartic acid, 6384-92-5; 4 aminobutyric acid, 28805-76-7, 56-12-2; hydrogen peroxide, 7722-84-1; gamma-Aminobutyric Acid; Glutamic Acid; Hydrogen Peroxide; Reactive Oxygen Species; Receptors, AMPA; Receptors, N-Methyl-D-Aspartate; Receptors, Purinergic P2X7 Funding details: Seventh Framework Programme, FP7, 294313 LA - English DB - MTMT ER -