Contractile responses of rat duodenum caused by transmural nerve stimulation: interaction between tachykininergic and...

We have studied the importance of tachykinins and acetylcholine for motor stimulation of the rat duodenum in vitro. Contractions induced by transmural nerve stimulation and tachykinin receptor agonists selective for NK1, NK2 and NK3 receptors were used in combination with a neurokinin (NK)2 receptor antagonist, MEN 10,627, and atropine as a muscarinic 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(-8) M) completely inhibited the response to transmural nerve stimulation (P < 0.001). As control, atropine alone reduced this response only by about 65%. Of the tachykinin analogues, [beta-AlaB]-neurokinin A(4-10) selective for NK2 receptors caused concentration-dependent contractions with high potency (pD2 8.01) and high efficacy, while substance P methyl ester acting on NK1 receptors had lower potency (pD2 7.94) and low efficacy, and senktide acting on NK3 receptors had a low potency (pD2 7.52) but high efficacy. With increasing concentrations of MEN 10,627 the response to [beta-AlaB]-neurokinin A(4-10) was markedly reduced (P < 0.01), while responses to substance P methyl ester and senktide were only slightly affected. Our results indicate that the physiological contractile responses of the rat duodenum are co-mediated by acetylcholine and tachykinins, for which NK2 receptors seem to be most important.