The influence of substance P on the response of guinea-pig isolated ileum to periarterial nerve stimulation.

1 The effects of substance P (SP) on the responses of the guinea-pig isolated ileum to periarterial nerve stimulation were studied. Electrical stimulation (2-50 Hz) of mesenteric periarterial nerves resulted in contraction of preparations pretreated with guanethidine. The responses were abolished by atropine and morphine, but unaffected by hexamethonium. 2 SP in a high concentration (0.65 mumol) inhibited reversibly, by about 40%, the responses of the guinea-pig isolated ileum to periarterial nerve stimulation. 3 SP in a very low concentration (0.18 pmol) potentiated (by about 20%) the responses of the guinea-pig isolated ileum to periarterial nerve stimulation. 4 In the presence of low concentrations (0.06-0.32 pmol) of SP, morphine (2.65 mumol) produced less inhibition of the responses to periarterial nerve stimulation, and recovery from morphine inhibition of contraction was accelerated. 5 These results indicate that SP may act as a modulator on prejunctional acetylcholine release in the guinea-pig ileum.