title: Effects of muscarinic receptor antagonists on acetylcholine-induced contractions of jejunal smooth muscle in horses.
abstract: This study investigated the effects of a muscarinic type 1 (M(1)), 2 (M(2)), and 3 (M(3)) antagonists (4-DAMP, pirenzepine, and methoctramine, respectively) on acetylcholine (Ach)-induced contractions of longitudinal jejunal muscle strips of horses. Strips were irrigated with Krebs-Henseleit solution gassed with 95% O(2) and 5% CO(2), and the developed tension in response to Ach was recorded before and after incubation with increasing concentrations of 4-DAMP (10(-8)-10(-6) M), pirenzepine (10(-6)-10(-4) M), and methoctramine (10(-5)-10(-3) M). When competitive antagonism was characterized, the affinity constant (pA(2)) was calculated by Schild plots. A parallel rightward shift in the concentration-response curves was observed after 4-DAMP and pirenzepine. Methoctramine presented a dual effect on the concentration-response curves: lower concentrations induced a parallel rightward shift without altering the maximum intensity of contraction (E(max)), while the highest concentration increased slope of the concentration-response curve and increased E(max). The pA(2) for 4-DAMP and pirenzepine was 9.18 and 7.13, respectively. Acetylcholine-induced contractions of longitudinal jejunal smooth muscle are mediated mainly via M(3) receptors. The complex role of M(2) receptors in jejunal smooth muscle contractions was evident because methoctramine potentiated the contractile response to higher doses of Ach.
authors.affiliation: Departmento de Cirurgia e Anestesiologia Veterinária, Faculdade de Medicina Veterinária e Zootecnia, Universidade Estadual Paulista, Botucatu, SP, Brazil. fteixeira@fmvz.unesp.br
authors.forename: F J
authors.initials: FJ
authors.lastname: Teixeira-Neto
authors.forename: W N
authors.initials: WN
authors.lastname: McDonell
authors.forename: W D
authors.initials: WD
authors.lastname: Black
authors.forename: W
authors.initials: W
authors.lastname: Harris
authors.forename: L
authors.initials: L
authors.lastname: Grovum
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D018679:Cholinergic Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006736:Horses; D007583:Jejunum / Q000187:drug effects* / Q000502:physiology*; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D013997:Time Factors
chemical_list: D018679:Cholinergic Agonists; D018727:Muscarinic Antagonists; D000109:Acetylcholine