CONTRACTILE RESPONSES OF RAT DUODENUM CAUSED BY TRANSMURAL NERVE-STIMULATION - INTERACTION BETWEEN TACHYKININERGIC AND CHOLINERGIC MECHANISMS

We have studied the importance of tachykinins and acetylcholine for mo tor stimulation of the rat duodenum in vitro. Contractions induced by transmural nerve stimulation and tachykinin receptor agonists selectiv e for NK1. NK2 and NK3 receptors were used in combination with a neuro kinin (NK)2 receptor antagonist. MEN 10.627, and atropine as a muscari nic receptor antagonist. Transmural nerve stimulation in the range 0.5 -32 Hz caused frequency-dependent contractions. MEN 10.627 (10(-8), 10 (-7) and 10(-6) M) dose-dependently reduced the contractile frequency- response curve (P < 0.01-0.001). Addition of atropine (10(-6) M) compl etely inhibited the response to transmural nerve stimulation (P < 0.00 1). ns control, atropine alone reduced this response only by about 65% . Of the tachykinin analogues. [beta-Ala(8)]-neurokinin A(4-10) select ive for NK2 receptors caused concentration-dependent contractions with high potency (pD(2) 8.01) and high efficacy, while substance P methyl ester acting on NK1 receptors had lower potency (pD(2) 7.94) and low efficacy, and senktide acting on NK3 receptors had a low potency (pD(2 ) 7.52) but high efficacy. With increasing concentrations of MEN 10.62 7 the response to [beta-Ala(8)]-neurokinin A(4-10) was markedly reduce d (P < 0.01), while responses to substance P methyl ester and senktide were only slightly affected. Our results indicate that the physiologi cal contractile responses of the rat duodenum are co-mediated by acety lcholine and tachykinins, for which NK2 receptors seem to be most impo rtant.