Undeca- and octa-peptide antagonists for substance P, a study on the guinea pig trachea.
Undeca - and octa-peptide analogues of substance P (SP), acting as antagonists in the guinea pig ileum, have been tested on the guinea pig trachea. The antagonistic properties of several octapeptides, particularly of [pro4, trp7 ,9,10,Phe11]SP-(4-11) have been confirmed, while the undecapeptides have been found to be potent stimulants of the trachea. The contractions of the guinea pig trachea in response several undecapeptides , particularly [pro2, trp7 ,9, Leu11 ]SP, undergo rapid tachyphylaxis, are significantly reduced in the presence of diphenhydramine and are not influenced by octapeptide antagonists of SP. These contractions appear to be due to the activation of tissue sites mediating the release of intramural histamine and different from SP receptors. On repeated applications, the stimulant effects of undecapeptides are eliminated and the compounds can be tested as antagonists. Undecapeptide antagonists have been found to be more potent against eledoisin and kassinin than against SP or physalaemin, while the octapeptides are equally active against the four homologues. Both undeca - and octa-peptides seem however to exert a competitive type of antagonism against all the SP-related peptides tested in the present study. Differences of antagonistic affinities have been interpreted as indicative of the existence of two different receptor types for SP and related peptides in the guinea pig trachea. The two receptors are blocked by the octapeptide antagonists, which are not discriminatory, while undecapeptides are particularly active on the receptor subtype which shows high sensitivity for eledoisin and kassinin .
D000818:Animals; D004155:Diphenhydramine / Q000494:pharmacology; D004600:Eledoisin / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology; D010803:Physalaemin / Q000494:pharmacology; D013373:Substance P / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors*; D014132:Trachea / Q000187:drug effects
D010455:Peptides; D010803:Physalaemin; D013373:Substance P; D004600:Eledoisin; D004155:Diphenhydramine