In vitro effects of bethanechol on equine gastrointestinal contractility and functional characterization of involved muscarinic receptor subtypes.
The goal of this study was to investigate the effect of bethanechol (BeCh) on contractility patterns of smooth muscle preparations of equine duodenum descendens, jejunum, caecum and pelvic flexure in vitro. Concentration-response relationships were developed for BeCh using in vitro assays with and without preincubation of muscarinic (M) receptor antagonists for M2 and M3 receptors. BeCh induced a significant, concentration-dependent increase in contractile response in equine intestine in specimens with circular orientation. The maximal effect was largest for jejunal specimens with no difference in EC50 within the different locations investigated. The M2 antagonist, AF-DX 116, caused a rightward shift of the concentration-response curve and the M3 antagonist, 4-DAMP (1,1-dimethyl-4-diphenylacetoxypiperidinium iodide), almost completely inhibited the effect of BeCh over the entire concentration-response curve. These data provide evidence that, although the effect of BeCh is predominantly mediated by M3 receptors, M2 muscarinic receptors also play a role in BeCh-induced contraction in specimens of equine intestine. The involvement of other muscarinic receptor subtypes cannot be excluded. Further studies are necessary to understand the effect of BeCh in vivo including diseased animals.
Marti
M
M
Clinic for Ruminants, Department of Clinical Veterinary Medicine and Division of Veterinary Pharmacology and Toxicology, University of Berne, Berne, Switzerland.
Mevissen
M
M
Althaus
H
H
Steiner
A
A
D000818:Animals; D019540:Area Under Curve; D018723:Bethanechol / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D002432:Cecum / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000187:drug effects; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006736:Horses / Q000378:metabolism; D007583:Jejunum / Q000187:drug effects; D008297:Male; D018721:Muscarinic Agonists / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D018727:Muscarinic Antagonists; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D017773:Pelvic Floor; D010890:Pirenzepine / Q000031:analogs & derivatives; D011976:Receptors, Muscarinic / Q000187:drug effects*
D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D018723:Bethanechol; D010890:Pirenzepine; C048593:otenzepad