The pharmacological profile of a substance P (SP) antagonist. Evidence for the existence of subpopulations of SP receptors.
The purpose of this study was to evaluate the pharmacological properties of a substance P (SP) analogue [D-Arg, D-Pro, D-Trp, Leu]SP as an SP antagonist. This analogue, blocked the SP-induced contractions of the isolated guinea-pig ileum and the rat urinary bladder and it exhibited no spasmogenic activity on these preparations. The affinity constant (pA2) for [D-Arg, D-Pro, D-Trp, Leu]SP versus SP was 6.31 on the guinea-pig ileum preparation and 5.30 on the rat urinary bladder preparation. The slopes of the regression lines of the Schild plots were close to unity. These data indicate that [D-Arg, D-Pro, D-Trp, Leu]SP blocks SP receptors in a simple competitive manner and suggest that there are at least two subpopulations of SP receptors. The contractions caused by the closely related tachykinins eledoisin and physalaemin were also blocked by the SP analogue. However, the slopes of the regression lines were significantly different from unity. Moreover, when tested on the hamster urinary bladder, which contracts at low concentrations of eledoisin but is rather insensitive to physalaemin and SP, [D-Arg, D-Pro, D-Trp, Leu]SP did not block the contractile actions of eledoisin or of physalaemin and SP. Compared to SP eledoisin and physalaemin may bind to SP receptors in a different manner. Eledoisin also seems to interact with receptors different from the SP receptors.
D000818:Animals; D006224:Cricetinae; D004600:Eledoisin / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D010803:Physalaemin / Q000494:pharmacology; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects*; D018040:Receptors, Neurokinin-1; D013373:Substance P / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects
D011956:Receptors, Cell Surface; D018040:Receptors, Neurokinin-1; D010803:Physalaemin; D013373:Substance P; D004600:Eledoisin; C038073:substance P, Arg(1)-Pro(2)-Trp(7),(9)-LeuNH(2)(11)-