Effect of substance P on right colonic pressure: a dose response study in pigs

The purpose of the present investigation was to elucidate the influence and mechanism of the action of substance P (SP) upon intraluminal pressure in proximal porcine colon. In 9 pigs, SP was infused intra-arterially in varying doses from 0.5 to 160 ng/kg/min. Mean baseline colonic pressure was 8.9 mm Hg increasing in a dose-dependent manner to 34.6 mm Hg at an SP dose of 40 ng/kg/min. Hereafter, the colonic pressure remained constant. In other series, SP infusion (5-80 ng/kg) was preceded by infusion of hexamethonium (0.5 mg/kg/min, continuous i.v.; n = 7), atropine (0.01 mg/kg/30 min, i.v.; n = 6), by naloxone (0.01 mg/kg/15 min, i.a.; n = 5) or tetrodotoxin (1 microgram/kg/h, i.a.; n = 7). Atropine significantly inhibited the effect of SP on colonic pressure, whereas the other blockers were without influence on the SP-induced colonic pressure. It is concluded that SP has a potent dose-dependent stimulatory effect upon right colonic intraluminal activity of the pig, mediated partly by atropine-sensitive receptors.