The novel opioid antagonist [dially-Tyr1,(CH2)S-Phe4,Leu5]enkephalin (M154,129) was examined for its ability to block the antisecretory effects of [D-Ala2,D-Leu5]enkephalin (DADLE) in isolated mucosal segments of the guinea-pig ileum, actions mediated predominantly through the δ opiate receptor. DADLE reduced transepithelial potential difference and short-circuit current (ED50 18 nM); these effects were competitively antagonized by M154,129 with a Ke value of 746 nM. These results are consistent with others demonstrating that M154,129 is a relatively selective although not highly potent blocker of δ opiate receptors.
Bibliographical noteFunding Information:
This work is supported in part by U.S.P.H.S. grant DA-02121 and an Alfred P. Sloan Fellowship to R.J.M. and by N.I.M.H. Postdoctoral Training Fellowship MH 14274 to D.R.B. We thank Dr. Michael Turnbull (ICI Pharmaceuticals) for the gift of M154,129 and Dr. David C. Draper (Department of Statistics, University of Chicago) for his assistance in the data analysis.
- δ Opiate receptor Intestinal electrolyte transport