Endothelin-Induced Nociception in Mice: Mediation by ETA and ETB Receptors

Er-i [1-38], big-ET-2[1-37] or big-ET-3[1-41]) injected i.p. in mice have previously been shown to elicit a characteristic no-ciceptive behavioral response. In this study, we investigated the endothelin receptor type (ETA or ETA) that mediates this behavioral response. Mice were injected i.p. with Er-i, ET-2, ET-3, big-ET-1[1-38], big-ET-2[1-37], big-ET-3[1-41], sarafo-toxin 56a, sarafotoxin S6b, sarafotoxin S6c, ET-1 with Ala substitutions for Cys3 and or His-Leu-Asp-lle-lle-Trp, and quantal dose-response curves were obtained for each of the compounds (except the latter). Co-administration of en-zyme inhibitors with the big-endothelins was used to establish the requisite conversion to endothelins and big-El-i [22-38], bmg-ET-2[22-37] and ET-3[22-41] amide, and the ETA-selective antagonist cyclo[-D-Asp-Pro-D-Val-Leu-D-Trp-] was used to de-termine receptor specificity. The ED50 values were 2.9, 3.3 an