TY - CHAP AU - Pethő, Gábor AU - Szolcsányi, János ED - Gyires, Klára ED - Fürst, Zsuzsanna ED - Ferdinandy, Péter ED - Pintér, Erika ED - Szilvássy, Zoltán ED - Varró, András TI - Helyi hormonok (autakoidok): hisztamin, antihisztaminok, szerotoninreceptor-agonisták és -antagonisták, prosztaglandinok T2 - Farmakológia és klinikai farmakológia PB - Medicina Könyvkiadó CY - Budapest SN - 9782632267388 PY - 2020 SP - 644 EP - 664 PG - 21 UR - https://m2.mtmt.hu/api/publication/32020552 ID - 32020552 LA - Hungarian DB - MTMT ER - TY - CHAP AU - Payrits, Maja AU - Ádám, Horváth AU - Biró-Sütő, Tünde AU - János, Erostyák AU - Géza, Makkai AU - Sághy, Éva AU - Pohóczky, Krisztina AU - Kecskés, Angéla AU - Kecskés, Miklós AU - Szolcsányi, János AU - Helyes, Zsuzsanna AU - Szőke, Éva ED - Rakonczay, Zoltán ED - Kiss, Lóránd TI - Resolvin D1 and D2 inhibit Transient Receptor Potential Vanilloid 1 and Ankyrin 1 Ion Channel activation on sensory neurons via lipid raft modification T2 - Proceedings of the EFOP-3.6.2-16-2017-00006 (LIVE LONGER) project PB - University of Szeged CY - Szeged SN - 9789633067642 PY - 2020 SP - 59 EP - 59 PG - 1 UR - https://m2.mtmt.hu/api/publication/31684068 ID - 31684068 LA - English DB - MTMT ER - TY - JOUR AU - Szőke, Éva AU - Horvath, Adam AU - Biró-Sütő, Tünde AU - Sághy, Éva AU - Payrits, Maja AU - Erostyák, János AU - Makkai, Géza AU - Szolcsányi, János AU - Helyes, Zsuzsanna TI - In vitro and in vivo evidence for the role of lipid rafts in Ca2+-gating of the Transient Receptor Potential channels in sensory neurons JF - FASEB JOURNAL J2 - FASEB J VL - 34 PY - 2020 IS - S1 PG - 2 SN - 0892-6638 DO - 10.1096/fasebj.2020.34.s1.05167 UR - https://m2.mtmt.hu/api/publication/31625361 ID - 31625361 LA - English DB - MTMT ER - TY - JOUR AU - Szőke, Éva AU - Bálint, Mónika Enikő AU - Hetényi, Csaba AU - Markovics, Adrienn AU - Elekes, Krisztián AU - Pozsgai, Gábor AU - Szűts, Tamás AU - Kéri, György AU - Őrfi, László AU - Sándor, Zoltán AU - Szolcsányi, János AU - Pintér, Erika AU - Helyes, Zsuzsanna TI - Small molecule somatostatin receptor subtype 4 (sst4) agonists are novel anti-inflammatory and analgesic drug candidates JF - NEUROPHARMACOLOGY J2 - NEUROPHARMACOLOGY VL - 178 PY - 2020 PG - 11 SN - 0028-3908 DO - 10.1016/j.neuropharm.2020.108198 UR - https://m2.mtmt.hu/api/publication/31396188 ID - 31396188 N1 - * Megosztott szerzőség AB - We provided strong proof of concept evidence that somatostatin mediates potent analgesic and anti-inflammatory actions via its receptor subtype 4 (sst4) located both at the periphery and the central nervous system. Therefore, sst4 agonists are promising novel drug candidates for neuropathic pain and neurogenic inflammation, but rational drug design was not possible due to the lack of knowledge about its 3-dimensional structure. We modeled the sst4 receptor structure, described its agonist binding properties, and characterized the binding of our novel small molecule sst4 agonists (4-phenetylamino-7H-pyrrolo[2,3-d]pyrimidine derivatives) using an in silico platform. In addition to the in silico binding data, somatostatin displacement by Compound 1 was demonstrated in the competitive binding assay on sst4-expressing cells. In vivo effects were investigated in rat models of neurogenic inflammation and chronic traumatic neuropathic pain. We defined high- and low-affinity binding pockets of sst4 for our ligands, binding of the highest affinity compounds were similar to that of the reference ligand J-2156. We showed potent G-protein activation with the highest potency of 10 nM EC50 value and highest efficacy of 342%. Oral administration of 100 μg/kg of 5 compounds significantly inhibited acute neurogenic plasma protein extravasation in the paw skin by 40-60%, one candidate abolished and 3 others diminished sciatic nerve-ligation induced neuropathic hyperalgesia by 28-62%. The in silico predictions on sst4-ligands were tested in biological systems. Low oral dose of our novel agonists inhibit neurogenic inflammation and neuropathic pain, which opens promising drug developmental perspectives for these unmet medical need conditions. LA - English DB - MTMT ER - TY - JOUR AU - Payrits, Maja AU - Horváth, Ádám AU - Biró-Sütő, Tünde AU - Erostyák, János AU - Makkai, Géza AU - Sághy, Éva AU - Pohóczky, Krisztina AU - Kecskés, Angéla AU - Kecskés, Miklós AU - Szolcsányi, János AU - Helyes, Zsuzsanna AU - Szőke, Éva TI - Resolvin D1 and D2 inhibit transient receptor potential vanilloid 1 and ankyrin 1 ion channel activation on sensory neurons via lipid raft modification JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 21 PY - 2020 IS - 14 PG - 17 SN - 1661-6596 DO - 10.3390/ijms21145019 UR - https://m2.mtmt.hu/api/publication/31387590 ID - 31387590 N1 - Funding Agency and Grant Number: National Brain Research Program [2017-1.2.1-NKP-2017-00002]; Hungarian Government [GINOP-2.3.2-15-2016-00050, EFOP-3.6.2-16-2017-00006, EFOP-3.6.2-16-2017-00008]; Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences; University of Pecs [17886-4/23018/FEKUTSTRAT]; New National Excellence Program of the ministry of Human Capacities [UNKP-18-4]; New National Excellence Program of the ministry for Innovation and Technology [UNKP-19-4] Funding text: This work was supported by the National Brain Research Program 2017-1.2.1-NKP-2017-00002 (NAP-2; Chronic Pain Research Group). We acknowledge the grant of the Hungarian Government (GINOP-2.3.2-15-2016-00050, EFOP-3.6.2-16-2017-00006 and EFOP-3.6.2-16-2017-00008). E. Szoke A. Kecskes and E. Saghy were supported by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences. The University of Pecs is acknowledged for a support by the 17886-4/23018/FEKUTSTRAT excellence grant. M. Payrits was supported by the New National Excellence Program of the ministry of Human Capacities UNKP-18-4. E. Szoke and E. Saghy were supported by the New National Excellence Program of the ministry of Human Capacities UNKP-18-4 and New National Excellence Program of the ministry for Innovation and Technology UNKP-19-4 grant. AB - Transient Receptor Potential Vanilloid 1 and Ankyrin 1 (TRPV1, TRPA1) cation channels are expressed in nociceptive primary sensory neurons and regulate nociceptor and inflammatory functions. Resolvins are endogenous lipid mediators. Resolvin D1 (RvD1) is described as a selective inhibitor of TRPA1-related postoperative and inflammatory pain in mice acting on the G protein-coupled receptor DRV1/GPR32. Resolvin D2 (RvD2) is a very potent TRPV1 and TRPA1 inhibitor in DRG neurons, and decreases inflammatory pain in mice acting on the GPR18 receptor, via TRPV1/TRPA1-independent mechanisms. We provided evidence that resolvins inhibited neuropeptide release from the stimulated sensory nerve terminals by TRPV1 and TRPA1 activators capsaicin (CAPS) and allyl-isothiocyanate (AITC), respectively. We showed that RvD1 and RvD2 in nanomolar concentrations significantly decreased TRPV1 and TRPA1 activation on sensory neurons by fluorescent calcium imaging and inhibited the CAPS-and AITC-evoked45Ca-uptake on TRPV1-and TRPA1-expressing CHO cells. Since CHO cells are unlikely to express resolvin receptors, resolvins are suggested to inhibit channel opening through surrounding lipid raft disruption. Here, we proved the ability of resolvins to alter the membrane polarity related to cholesterol composition by fluorescence spectroscopy. It is concluded that targeting lipid raft integrity can open novel peripheral analgesic opportunities by decreasing the activation of nociceptors. © 2020 by the authors. Licensee MDPI, Basel, Switzerland. LA - English DB - MTMT ER - TY - JOUR AU - Borbély, Éva AU - Kiss, Tamás AU - Szabadfi, Krisztina AU - Pintér, Erika AU - Szolcsányi, János AU - Helyes, Zsuzsanna AU - Botz, Bálint TI - Complex Role of Capsaicin-Sensitive Afferents in the Collagen Antibody-Induced Autoimmune Arthritis of the Mouse JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 8 ET - 0 PY - 2018 IS - 1 PG - 8 SN - 2045-2322 DO - 10.1038/s41598-018-34005-6 UR - https://m2.mtmt.hu/api/publication/30306941 ID - 30306941 N1 - * Megosztott szerzőség AB - Capsaicin-sensitive afferents have complex regulatory functions in the joints orchestrated via neuropeptides. This study aimed to determine their role in the collagen-antibody induced rheumatoid arthritis model. Capsaicin-sensitive nerves were defunctionalized by the capsaicin receptor agonist resiniferatoxin in C57Bl/6 mice. Arthritis was induced by the ArithroMab antibody cocktail and adjuvant. Arthritis was monitored by measuring body weight, joint edema by plethysmometry, arthritis severity by clinical scoring, mechanonociceptive threshold by plantar esthesiometry, thermonociceptive threshold by hot plate, cold tolerance by paw withdrawal latency from 0 °C water. Grasping ability was determined by the wire-grid grip test. Bone structure was evaluated by in vivo micro-CT and histology. Arthritic animals developed a modest joint edema, mechanical and cold hyperalgesia, weight loss, and a diminished grasping function, while thermal hyperalgesia is absent in the model. Desensitised mice displayed reduced arthritis severity, edema, and mechanical hyperalgesia, however, cold hyperalgesia was significantly greater in this group. Arthritic controls displayed a transient decrease of bone volume and an increased porosity, while bone density and trabecularity increased in desensitised mice. The activation of capsaicin-sensitive afferents increases joint inflammation and mechanical hyperalgesia, but decreases cold allodynia. It also affects inflammatory bone structural changes by promoting bone resorption. LA - English DB - MTMT ER - TY - JOUR AU - Sághy, Éva AU - Payrits, Maja AU - Biro-Suto, T AU - Skodáné Földes, Rita AU - Szánti-Pintér, Eszter AU - Erostyák, János AU - Makkai, Géza AU - Sétáló, György (ifj.) AU - Kollár, László AU - Kőszegi, Tamás AU - Jakabfi-Csepregi, Rita AU - Szolcsányi, János AU - Helyes, Zsuzsanna AU - Szőke, Éva TI - Carboxamido steroids inhibit the opening properties of Transient Receptor Potential ion channels by lipid raft modulation. JF - JOURNAL OF LIPID RESEARCH J2 - J LIPID RES VL - 59 PY - 2018 IS - 10 SP - 1851 EP - 1863 PG - 13 SN - 0022-2275 DO - 10.1194/jlr.M084723 UR - https://m2.mtmt.hu/api/publication/3402940 ID - 3402940 N1 - * Megosztott szerzőség AB - Transient Receptor Potential (TRP) cation channels, like the TRP Vanilloid 1 and TRP Ankyrin 1 (TRPV1 and TRPA1) are expressed on primary sensory neurons. These thermosensor channels play role in pain processing. We provided evidence that lipid raft disruption influenced the TRP channel activation and a carboxamido-steroid compound (C1) inhibited TRPV1 activation. Therefore, our aim was to investigate whether this compound exerts its effect through lipid raft disruption and the steroid backbone (C3) or altered position of the carboxamido group (C2) influence the inhibitory action by measuring Ca2+-transients on isolated neurons and calcium-uptake on receptor-expressing CHO cells. Membrane cholesterol content was measured by filipin staining and membrane polarisation by fluorescence spectroscopy. Both the percentage of responsive cells and the magnitude of the intracellular Ca2+-enhancement evoked by the TRPV1 agonist capsaicin were significantly inhibited after C1 and C2 incubation, but not after C3 administration. C1 was able to reduce other TRP channel activation as well. The compounds induced cholesterol depletion in CHO cells, but only C1 induced changes in membrane polarisation. The inhibitory action of the compounds on TRP channel activation develops by lipid raft disruption, and the presence and the position of the carboxamido group is essential. LA - English DB - MTMT ER - TY - JOUR AU - Tóth, Eszter AU - Tornóczky, Tamás AU - Kneif, Józsefné AU - Perkecz, A AU - Katona, Krisztián AU - Piski, Zalán AU - Kemény, Ágnes AU - Gerlinger, Imre AU - Szolcsányi, János AU - Kun, József AU - Pintér, Erika TI - Upregulation of extraneuronal TRPV1 expression in chronic rhinosinusitis with nasal polyps JF - RHINOLOGY J2 - RHINOLOGY VL - 56 PY - 2018 IS - 3 SP - 245 EP - 254 PG - 10 SN - 0300-0729 DO - 10.4193/Rhin17.108 UR - https://m2.mtmt.hu/api/publication/3339990 ID - 3339990 N1 - * Megosztott szerzőség AB - BACKGROUND: Chronic rhinosinusitis (CRS) is a multifactorial upper airway disease with unclear etiology. Neuronal Transient Receptor Potential Vanilloid 1 (TRPV1) and Ankyrin 1 (TRPA1) channels have been implicated in the pathogenesis of CRS. We aimed to detect the expression of extraneuronal TRPV1 and TRPA1 receptors in nasal polyp (NP) tissue samples. METHODOLOGY: Samples were obtained from fourty-two CRS pateints with nasal polyp and sixteen healthy controls to measure receptor gene expression by quantitative PCR, protein localization by immunohistochemistry and cytokine profile by multiplex bead immunoassay. RESULTS: Non-neuronal TRPV1, TRPA1 receptors were expressed in biopsy samples of NP. A population of mast cells and macrophages were immunopositive for TRPV1 and TRPA1. A fraction of plasma cells expressed TRPV1 but not TRPA1 and neither receptor was present on eosinophils. The local gene expression of extraneuronal TRPV1, TRPA1 receptors was also proven. TRPV1 mRNA levels were significantly increased in CRSwNP patients with asthma and allergic rhinitis compared to their NP counterparts. CONCLUSIONS: Elevated TRPV1 levels in comorbid asthma and allergy may have a function in CRSwNP. Subpopulation-specific TRPV1 presence on plasma and mast cells can indicate delicate roles in regulating activation and release of inflammatory mediators. LA - English DB - MTMT ER - TY - JOUR AU - Karátson, András AU - Szolcsányi, János TI - Nils Alwall a művese egyik alaptípusának feltalálója és magyar kapcsolata JF - HYPERTONIA ÉS NEPHROLOGIA J2 - HYPERTONIA NEPHROLOGIA VL - 21 PY - 2017 IS - 1 SP - 44 EP - 48 PG - 5 SN - 1418-477X UR - https://m2.mtmt.hu/api/publication/3297015 ID - 3297015 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Payrits, Maja AU - Sághy, Éva AU - Csekő, Kata AU - Pohóczky, Krisztina AU - Bölcskei, Kata AU - Ernszt, Dávid AU - Barabás, Klaudia AU - Szolcsányi, János AU - Ábrahám, István AU - Helyes, Zsuzsanna AU - Szőke, Éva TI - Estradiol sensitizes the Transient Receptor Potential Vanilloid 1 receptor in pain responses JF - ENDOCRINOLOGY J2 - ENDOCRINOLOGY VL - 158 PY - 2017 IS - 10 SP - 3249 EP - 3258 PG - 10 SN - 0013-7227 DO - 10.1210/en.2017-00101 UR - https://m2.mtmt.hu/api/publication/3248672 ID - 3248672 N1 - Funding Agency and Grant Number: Hungarian Brain Research Program B (MTA-PTENAP-B) [KTIA_NAP_13-2014-0001]; Molecular Neuroendocrinology Research Groups; OTKA [112807]; Richter Gedeon Talentum Foundation; Ministry of HumanCapacities [UNKP-16-4-I]; Hungarian Academy of Sciences; [KTIA_NAP_13-2014-0022] Funding text: This work was supported by Hungarian grants KTIA_NAP_13-2014-0022 and Hungarian Brain Research Program B (KTIA_NAP_13-2014-0001, MTA-PTENAP-B) Chronic Pain (Z.H., E. Szoke) and by Molecular Neuroendocrinology Research Groups (I.M.A.) and OTKA (112807) (I.M.A.). K.C., M.P. and E. Saghy were supported by the Richter Gedeon Talentum Foundation. E. Saghy was supported by the UNKP-16-4-I NewNational Excellence Program of the Ministry of HumanCapacities. E. Szoke holds a Janos Bolyai Fellowship from the Hungarian Academy of Sciences. LA - English DB - MTMT ER -