Contractile effects of substance P and neurokinin A on the rat stomach in vivo and in vitro.

Substance P and neurokinin A (substance K) were infused into the coeliac artery of anaesthetized rats at doses of 0.06-20 nmol min-1. Both tachykinins caused contractions of the stomach, the threshold dose of neurokinin A being 10 times lower than of substance P. The dose-response curve for substance P was flatter than that for neurokinin A. On circular muscle strips from the rat gastric corpus in vitro, the dose-response curves for both tachykinins were parallel, neurokinin A being 10 times more potent than substance P. The contractions in response to 10 microM neurokinin A and to 30 microM substance P were 58 and 54%, respectively, of the maximal contraction to bethanechol (1 mM). The effect of substance P was reduced by atropine both in vivo and in vitro. In vitro, the contractions to substance P were also reduced by tetrodotoxin but left unaffected by methysergide. The action of neurokinin A was not affected by these drugs. It is concluded that neurokinin A contracts rat stomach by a direct action on the circular smooth muscle, whereas the action of substance P is mediated, at least in part, by cholinergic interneurones.