PROCTOLIN ANALOGS AND A PROCTOLIN METABOLITE AS ANTAGONISTS OF THE PEPTIDE PROCTOLIN

The locust oviduct bioassay was used to assess a variety of proctolin analogues as possible agonists and antagonists of the peptide proctoli n. Both [alpha-methyl-L-tyrosine(2)] proctolin and [N-methyl-L-tyrosin e(2)] proctolin were agonists of proctolin with thresholds of 5 X 10(- 9) M. Interestingly, at these threshold doses the analogues were antag onists when applied along with proctolin, being capable of shifting th e dose-response curve for proctolin an order of magnitude to the right . Of the three tripeptides tested Tyr-Arg-Thr and Arg-Tyr-Thr showed n o agonistic effects and were incapable of antagonizing proctolin-induc ed contractions. The third tripeptide, Leu-Pro-Thr, showed minimal ago nistic effects and when applied with proctolin, significantly decrease d the maximum response and increased the ED50 values of the parent com pound. Interestingly, this tripeptide is a degradation product of proc tolin. Cycloproctolin possessed no agonistic activity up to 10(-5) M b ut did antagonize proctolin's response in a dose-dependent manner with 2 X 10(-5) M cycloproctolin shifting the proctolin curve nearly two o rders of magnitude to the right. Simultaneous application of 10(-9) M [alpha-methyl-L-tyrosine(2)] proctolin and 10(-5) M cycloproctolin sho wed some synergistic effect as the maximum response to the peptide was decreased by 21.6% and the dose-response curve shifted further to the right. These proctolin antagonists will be useful tools for examining the physiological importance of proctolin in insects as well as helpi ng to identify receptor subtypes. (C) 1997 Elsevier Science Inc.