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Pharmacological identification of acetylcholine receptor subtypes in echinoderm smooth muscle (Sclerodactyla briareus)
Institution:1. Department of Respiratory Geriatrics, Chongqing Public Health Medical Center, Shapingba, 400000, Chongqing, China;2. Department of Cardiothoracic Surgery, Chongqing Southwest Hospital, Shapingba, 400000, Chongqing, China;3. Department of Medicine, Chongqing Jalin Hospital, Shapingba, 400000, Chongqing, China;5. Department of Anesthesiology, Chongqing Public Health Medical Center, Shapingba, 400000, Chongqing, China;1. CEA, Institute of Biology and Technology (iBiTecS), Service d''Ingénierie Moléculaire des Protéines (SIMOPRO), Gif-sur-Yvette 91191, France;2. UFR Sciences de la Vie, Université Pierre et Marie Curie (UPMC), 4 place Jussieu, Paris, France;3. CNRS, IRISA, Campus de Beaulieu, 35042 Rennes, France;1. Division of Preclinical Research, Egis Pharmaceuticals PLC, Budapest, Hungary;2. Chemical Research Division, Egis Pharmaceuticals PLC, Budapest, Hungary;3. Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary;4. Division of Neuroscience, Medical Research Institute, Ninewells Hospital and Medical School, Dundee University, Dundee DD19SY, Scotland, UK;5. Institut de Recherches Servier, Croissy-sur-Seine, France;1. Department of Civil Engineering, University of Thessaly, Pedion Areos, Gr-38334 Volos, Greece;2. Department of Energy Technology Engineering, Technological & Educational Institute of Athens, Agiou Spiridonos 17, 12210 Athens, Greece
Abstract:Contractions of an echinoderm (sp. Sclerodactyla briareus) smooth muscle, the longitudinal muscle of the body wall (LMBW), were evoked by acetylcholine (ACh) and agonists: epibatidine, muscarine and nicotine (in order of force generation: ACh>muscarine=epibatidine>nicotine). ACh-induced contractions were blocked by atropine by 50%, and methoctramine, by 30%. ACh responses were also blocked by 25% by methyllycaconitine (MLA) but not by d-tubocurarine (dTC). Muscarine initiated large contractions that were completely blocked by atropine. To elucidate possible muscarinic ACh receptor (mAChR) subtypes, muscarinic agonists (oxotremorine, pilocarpine) and antagonists (methoctramine, pirenzepine) were tested. Oxotremorine, pilocarpine, and pirenzepine each enhanced resting tonus and potentiated ACh-induced contractions (order of potency: pilocarpine>oxotremorine=pirenzepine). Muscarine, oxotremorine or pirenzepine generated phasic, rhythmic contractions. Nicotine-induced contractions were almost completely blocked by dTC but were not altered by atropine. Large contractions evoked by epibatidine were potentiated by dTC whereas atropine had no effect on them. MLA blocked spontaneous rhythmicity. Cholinesterase inhibitors, neostigmine or physostigmine, caused marked potentiation of ACh-induced contractions and initiated rhythmic slow wave contractions in previously quiescent muscles. The present pharmacological evidence points to the co-existence of excitatory nicotinic ACh receptor (nAChRs) and mAChRs where nAChRs possibly modulate tone, and the mAChRs initiate and enhance rhythmicity.
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