SUBSTANCE-P-INDUCED CONTRACTIONS OF THE GUINEA-PIG PROXIMAL COLON THROUGH STIMULATION OF POSTJUNCTIONAL TACHYKININ NK(1) RECEPTORS

The effects of three tachykinin NK1 receptor antagonists and a tachyki nin NK2 receptor antagonist against substance P-induced contractions o f the guinea-pig proximal colon longitudinal muscle were investigated. Atropine, tetrodotoxin and phosphoramidon did not affect the concentr ation-response curve for substance P (pEC50 = 7.8). The tachykinin NK1 receptor antagonist, 2S,3S-cis-CP 96345, competitively inhibited the contractions due to substance P (pA2 = 8.5; constrained pA2 = 8.9). bu t at higher concentrations (greater-than-or-equal-to 3 x 10(-7) M), 2S ,3S-cis-CP 96345 also depressed the concentration-response curve for m ethacholine. The species-selective tachykinin NK1 receptor antagonists , WIN 51708 and WIN 62577 (both 1 x 10(-6) M), and the tachykinin NK2 receptor antagonist, SR 48968 (3 x 10(-7) M), had no effect. It is con cluded that substance P induces contractions through the stimulation o f tachykinin NK1 receptors on the smooth muscle cells. In this prepara tion, tachykinin NK2 receptors do not seem to be involved in the contr actile action of substance P.