title: Pharmacologic characterization of muscarine receptor subtypes in rat gastric fundus mediating contractile responses.
abstract: The role of four muscarinic receptor subtypes M1, M2, M3 and M4 which have been characterized pharmacologically was examined in motility control of isolated rat gastric fundus. Acetylcholine produced concentration-dependent tonic contraction of isolated rat fundus (EC50 = 9.64 +/- 0.14 x 10(-8)M). These contractions were concentration-dependently antagonized by atropine (KB = 2.45 x 10(-11)M), M1 selective blockers telenzepine (KB = 6.64 x 10(-11)M) and pirenzepine (KB = 2.3 x 10(-8)M), and hexocyclium (KB = 2.82 x 10(-10)M). M3-selective blocker p-fluoro-hexahydro-sila-difenidol (pFHHSiD) was a less potent antagonist (KB = 2.3 x 10(-8)M), while M2 and M4-selective methoctramine produced only weak blockade of tonic contractions caused by acetylcholine (KB = 4.68 x 10(-6)M). These results suggest that only M1 and M3 muscarinic receptors have functional roles in motility control of rat gastric fundus, M1 receptors being more important.
authors.affiliation: Department of Pharmacology, Medical Faculty, University of Kragujevac, Serbia, Yugoslavia.
authors.forename: D R
authors.initials: DR
authors.lastname: Milovanović
authors.forename: S M
authors.initials: SM
authors.lastname: Janković
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D003959:Diamines / Q000494:pharmacology; D005260:Female; D005748:Gastric Fundus / Q000502:physiology*; D005769:Gastrointestinal Motility / Q000502:physiology*; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000145:classification* / Q000502:physiology
chemical_list: D003959:Diamines; D018727:Muscarinic Antagonists; D010879:Piperazines; D010880:Piperidines; D011976:Receptors, Muscarinic; C046338:telenzepine; C058297:4-fluorohexahydrosiladifenidol; D010890:Pirenzepine; D001285:Atropine; C015922:hexocyclium; D000109:Acetylcholine; C054938:methoctramine