title: Pharmacological characterization of muscarinic receptors in the contractions of isolated bronchi in the horse.
abstract: We investigated the effects of nonselective muscarinic antagonist (atropine) and of selective muscarinic subtype 1 (M1), 2 (M2), 3 (M3) antagonists (VU0255035, methoctramine, pFHHSiD, respectively) on the contractions evoked by electrical field stimulation (EFS) or by exogenous ACh in isolated horse bronchial muscle. Atropine completely inhibited neurogenic contractions in a concentration-dependent fashion, whereas selective muscarinic antagonists induced relevant modifications only at the highest concentration tested. Experiments with selective muscarinic antagonists in combination showed that only the simultaneous blockade of M1 /M3 or M2 /M3 receptors was able to induce a nearly complete suppression of contractions. The contractions induced by exogenous ACh were competitively antagonized only by atropine (pA2 = 9.01 ± 0.05). M3 selective antagonist, up to 10(-6) m, caused a moderate concentration-dependent rightward shift of ACh curve (pA2 = 7.96 ± 0.10). These data show that M3 muscarinic receptors possess a central role in mediating cholinergic contraction of horse bronchi, while M1 and M2 receptors seem to have a cooperative role. Selective muscarinic antagonists seem unlikely to be useful against bronchoconstriction associated with airway diseases in horses. Conversely, compounds with selectivity for both M1 and M3 receptors could be as effective as traditional anticholinergics and induce fewer cardiac side effects.
authors.affiliation: Dipartimento di Scienze Medico-Veterinarie, Università di Parma, Parma, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Menozzi
authors.forename: C
authors.initials: C
authors.lastname: Pozzoli
authors.forename: E
authors.initials: E
authors.lastname: Poli
authors.forename: B
authors.initials: B
authors.lastname: Delvescovo
authors.forename: P
authors.initials: P
authors.lastname: Serventi
authors.forename: S
authors.initials: S
authors.lastname: Bertini
mesh_terms: D000818:Animals; D001980:Bronchi / Q000378:metabolism*; D001986:Bronchial Spasm / Q000188:drug therapy* / Q000378:metabolism; D003959:Diamines / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000502:physiology; D006736:Horses; D008297:Male; D010276:Parasympatholytics / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D043643:Receptor, Muscarinic M1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D043585:Receptor, Muscarinic M2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D043587:Receptor, Muscarinic M3 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D013830:Thiadiazoles / Q000494:pharmacology
chemical_list: D003959:Diamines; C542801:N-(3-oxo-3-(4-(pyridin-4-yl)piperazin-1-yl)propyl)benzo(c)(1,2,5)thiadiazole-4-sulfonamide; D010276:Parasympatholytics; D010880:Piperidines; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D013449:Sulfonamides; D013830:Thiadiazoles; C058297:4-fluorohexahydrosiladifenidol; C054938:methoctramine