MYOTROPIC EFFECTS OF PROCTOLIN ANALOGS, MODIFIED IN POSITION-2 OF THEPEPTIDE-CHAIN, ON THE FOREGUT OF THE LOCUST SCHISTOCERCA-GREGARIA

Proctolin (H.Arg.Tyr.Leu.Pro.Thr.OH) caused dose-dependent contraction of the isolated foregut of the locust Schistocerca gregaria at concen trations ranging from 10(-8) M to 2 x 10(-6) M, Of the ten analogues e valuated, [Phe(p-NH2)(2)]-, [Tyr(m-NH2)(2)]- and [Phe(p-OEt)(2)]-proct olin are dose-dependent supra agonists while [Phe(p-OMe)(2)]- and [L-D OPA(2)]-proctolin are supra agonists only when applied at a single dos e of 5 x 10(-7) M, Construction of dose response curves showed that [P he(p-OMe)(2)]-, [L-DOPA(2)]-, [Phe(p-NH2)(2)]- and [Phe(p-NO2)(2)]-pro ctolin are partial agonists incapable of causing a maximum response eq uivalent to that induced by the parent pentapeptide. [Cha(4-OMe)(2)]-, [Afb(p-OH)(2)]- and [Afb(p-NO2)(2)]-Proctolin are weak agonists with intrinsic activities equivalent to only 12.7%, 7.9% and 3.5% respectiv ely of that of proctolin, [alpha-Me-L-Tyr(2)]- and [Afb(p-NO2)(2)]-Pro ctolin (10(-8) M -10(-6) M) are potent non-competitive antagonists of proctolin induced tissue contraction, reducing the maximum response of applied proctolin to 16% and 23% respectively when used at a dose of 10(-6) M, From analysis of the myotropic effects of the analogues inve stigated in this study, we conclude that the agonist actions of procto lin are dependent on the presence of either a para substituted Phe or a meta substituted Tyr in position 2 of the peptide chain, These data show that the ideal substituents on the aromatic ring are groups conta ining oxygen and nitrogen atoms, Copyright (C) 1996 Elsevier Science L td