In vitro effects of bethanechol on intestinal smooth muscle preparations in presence and absence of M2 and M3 muscarinic receptor antagonists in healthy dairy cows

The aim of the present study was to investigate the in vitro effects of bethanechol (BeCh), a directly acting parasympathetic agonist, in presence and absence of M 2 (AF-DX 116) or M 3 (4-DAMP) muscarinic receptor antagonists, on bovine smooth muscle preparations (circular and longitudinal specimens) from the ileum, caecum, proximal loop of the ascending colon and spiral colon.Tissue samples were harvested at the slaughterhouse from healthy, lactating dairy cows (n = 10), preparations were suspended in individual organbaths, and the contractile effect after cumulative administration of BeCh was recorded. Concentration response curves (CRC), the maximal attainable response (V max ) and the effective concentration 50 % (EC 50 ) for BeCh were calculated for the parameters area under the curve, maximal amplitude of the contractions, and basal tone. Bethanechol produced a concentration-dependent increase of all parameters. After incubation with AF-DX 116, BeCh still produced a significant concentration-dependent increase of all parameters in specimens of all locations, and a rightward shift of the CRC. After incubation with 4-DAMP, the effect of BeCh was almost completely blocked, and the contractile effect remained minimal.The results of this study emphasize the therapeutic potential of BeCh in spontaneous cases of cacal dilatation/-dislocation, where enhancement of motility in the spiral colon is targeted.