ENDOMORPHIN-1 AND ENDOMORPHIN-2 ARE PARTIAL AGONISTS AT THE HUMAN MU-OPIOID RECEPTOR

Recently two tetrapeptide ligands that bind preferentially to the mu-o pioid receptor were identified and named endomorphin-1 and endomorphin -2. We examined the ability of these peptides to stimulate G protein a ctivation in human CL-opioid receptor transfected B82 fibroblasts as m easured by [S-35]GTP gamma S binding to cell membranes. Both endomorph in-1 and -2 act as partial agonists in this assay system compared with the mu-selective agonist [D-Ala(2),N-Me-Phe(4), Gly-ol(5)]enkephalin (DAMGO). In addition, endomorphins demonstrate efficacy similar to mor phine. These findings demonstrate that endomorphin peptides have simil ar activity at the mu-opioid receptor as morphine and suggest that the se peptides have the potential to modulate neuronal activity in vivo. (C) 1998 Elsevier Science B.V.