Suc-Tyr(SE)-Met-Gly-Trp-Met-Asp-beta-phenethylamide(410): a competitive antagonist of cholecystokinin-induced contractions in smooth muscles in vitro.

Suc-Tyr(SE)-Met-Gly-Trp-Met-Asp-beta-phenethylamide(410) has been studied for its ability to antagonize contractile responses of guinea pig gall bladder, ileum and stomach muscle strips to desamino-cholecystokinin-octapeptide (CCK-7) and cholecystokinin octapeptide (CCK-8). Both CCK-7 and CCK-8 at concentrations of 10(-11)M to 10(-7)M produced dose-dependent tonic contractions in all muscle strips. Suc-Tyr(SE)-Met-Gly-Trp-Met-Asp-beta-phenethylamide (10(-8)M-10(-5)M) inhibited reversibly in a dose-dependent manner the contractile responses to CCK-7 and CCK-8. At the same concentrations the antagonist shifted to the right in parallel to the dose-response curves for CCK-7 and CCK-8 without decreasing their maximum response. Analysis of the data after Schild gave pA2 values (410 potency as antagonist) of CCK-7 in gall bladder, ileum and stomach of 8.36; 8.0 and 7.56, respectively, and pA2 values of CCK-8 of 7.64; 8.94 and 8.52, respectively. The slope of the Schild plots for both CCKs did not differ significantly from the unity, which suggests that 410 is a competitive antagonist. The antagonistic action of 410 is reversible and appeared to be specific since at concentrations of 5 X 10(-6), it had no effect on contractile responses of the gall bladder, ileum and gastric muscle strips to acetylcholine or histamine.