Role of muscarinic receptors in the contraction of jejunal smooth muscle in the horse: An in vitro study

Segments of circular muscle of equine jejunum, were put into organ baths, connected to isotonic transducers, and the effects on ACh concentration-response curves, and on electrical field stimulation (EFS)-evoked contractions of intestinal preparations, induced by nonselective or selective MR antagonists, compared to pre-drug level, were studied. Atropine (nonselective MR antagonist), pirenzepine (selective M1 antagonist), and p-FHHSiD (selective M3 antagonist) competitively antagonized ACh (pA2 = 9.78 ± 0.21; 7.14 ± 0.25 and 7.56 ± 0.17, respectively). Methoctramine (selective M2 antagonist) antagonized ACh in a concentration-unrelated fashion; however, it competitively antagonized carbachol, a nonselective muscarinic agonist (pA2 = 6.42 ± 0.23). Atropine dose-dependently reduced EFS-evoked contractions, reaching a maximal effect of − 45.64 ± 6.54%; the simultaneous block of neurokinin receptors, almost completely abolished the atropine-insensitive contractions. p-FHHSiD dose-dependently reduced EFS-induced contractions, while pirenzepine caused a minor decrease. Methoctramine, ineffective up to 10− 7 M, enhanced the contractions at 10− 6 M; the block of neurokinin receptors abolished the increase of contraction. Cholinergic contractions of horse jejunum are mainly mediated by M3 receptors; M2 selective antagonists seem to scarcely affect cholinergic, and to enhance neurokininergic contractions of equine jejunum, thus their use entails a lower risk of causing intestinal hypomotility, compared to nonselective drugs.