Effects of muscarinic receptor antagonists on acetylcholine-induced contractions of jejunal smooth muscle in horses

Abstract

Teixeira-Neto, F. J., McDonell, W. N., Black, W. D., Harris, W., Grovum, L. Effects of muscarinic receptor antagonists on acetylcholine-induced contractions of jejunal smooth muscle in horses. J. vet. Pharmacol. Therap. 35, 313-318.This study investigated the effects of a muscarinic type 1 (M1), 2 (M2), and 3 (M3) 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% O2 and 5% CO2, and the developed tension in response to Ach was recorded before and after incubation with increasing concentrations of 4-DAMP (10-810-6 m), pirenzepine (10-610-4 m), and methoctramine (10-510-3 m). When competitive antagonism was characterized, the affinity constant (pA2) was calculated by Schild plots. A parallel rightward shift in the concentrationresponse curves was observed after 4-DAMP and pirenzepine. Methoctramine presented a dual effect on the concentrationresponse curves: lower concentrations induced a parallel rightward shift without altering the maximum intensity of contraction (Emax), while the highest concentration increased slope of the concentrationresponse curve and increased Emax. The pA2 for 4-DAMP and pirenzepine was 9.18 and 7.13, respectively. Acetylcholine-induced contractions of longitudinal jejunal smooth muscle are mediated mainly via M3 receptors. The complex role of M2 receptors in jejunal smooth muscle contractions was evident because methoctramine potentiated the contractile response to higher doses of Ach.