PHARMACOLOGY OF PROCTOLIN RECEPTORS IN THE ISOLATED FOREGUT OF THE LOCUST SCHISTOCERCA-GREGARIA - IDENTIFICATION OF [ALPHA-METHYL-L-TYROSINE(2)]-PROCTOLIN AS A POTENT RECEPTOR ANTAGONIST

1. Proctolin (H-Arg-Tyr-Leu-Pro-Thr-OH) caused dose-dependent contract ion of the foregut of the locust Schistocerca gregaria. 2. Of the nine new analogues tested, five stimulated tissue contraction, the most po tent being [p-fluoro-L-phenylalanine(2)]-proctolin which caused a maxi mum response 35% greater than that induced by proctolin. 3. The demons tration that [3'-mono-iodo-L-tyrosine(2)]-proctolin is a potent agonis t provides a physiological basis for the use of the [I-125] derivative of this peptide to study proctolin binding sites in insect tissues. 4 . The tripeptide Arg-Tyr-Thr was devoid of agonist action but reduced the myotropic activity of proctolin. 5. Cyclic proctolin and [alpha-me thyl-L-tyrosine(2)]-proctolin reduced the maximum response to proctoli n by 37 and 88%, respectively when used as antagonists at concentratio ns of 5 x 10(-6) and 10(-6) M, respectively. The demonstration that [a lpha-methy-L-tyrosine(2)]-proctolin is a potent proctolin receptor ant agonist means that it is now possible to characterize the receptors th at the parent pentapeptide activates to bring about its physiological effects.