In vitro effects of bethanechol on specimens of intestinal smooth muscle obtained from the duodenum and jejunum of healthy dairy cows.
OBJECTIVE
To describe the in vitro effects of bethanechol on contractility of smooth muscle preparations from the small intestines of healthy cows and define the muscarinic receptor subtypes involved in mediating contraction.


METHODS
Tissue samples from the duodenum and jejunum collected immediately after slaughter of 40 healthy cows.


METHODS
Cumulative concentration-response curves were determined for the muscarinic receptor agonist bethanechol with or without prior incubation with subtype-specific receptor antagonists in an organ bath. Effects of bethanechol and antagonists and the influence of intestinal location on basal tone, maximal amplitude (A(max)), and area under the curve (AUC) were evaluated.


RESULTS
Bethanechol induced a significant, concentration-dependent increase in all preparations and variables. The effect of bethanechol was more pronounced in jejunal than in duodenal samples and in circular than in longitudinal preparations. Significant inhibition of the effects of bethanechol was observed after prior incubation with muscarinic receptor subtype M(3) antagonists (more commonly for basal tone than for A(max) and AUC). The M(2) receptor antagonists partly inhibited the response to bethanechol, especially for basal tone. The M(3) receptor antagonists were generally more potent than the M(2) receptor antagonists. In a protection experiment, an M(3) receptor antagonist was less potent than when used in combination with an M(2) receptor antagonist. Receptor antagonists for M(1) and M(4) did not affect contractility variables.


CONCLUSIONS
Bethanechol acting on muscarinic receptor sub-types M(2) and M(3) may be of clinical use as a prokinetic drug for motility disorders of the duodenum and jejunum in dairy cows.
Pfeiffer
Julia B R
JB
Clinic for Ruminants, Vetsuisse Faculty, University of Berne, 3012 Berne, Switzerland.
Mevissen
Meike
M
Steiner
Adrian
A
Portier
Christopher J
CJ
Meylan
Mireille
M
D000818:Animals; D018723:Bethanechol / Q000494:pharmacology*; D002417:Cattle; D003612:Dairying; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D007583:Jejunum / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D010276:Parasympatholytics / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000494:pharmacology; D014331:Tropicamide / Q000494:pharmacology
D010276:Parasympatholytics; D010277:Parasympathomimetics; D010880:Piperidines; D018723:Bethanechol; D010890:Pirenzepine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D014331:Tropicamide; C048593:otenzepad