Endomorphin-1 and endomorphin-2 are partial agonists at the human μ-opioid receptor

Recently two tetrapeptide ligands that bind preferentially to the μ-opioid receptor were identified and named endomorphin-1 and endomorphin-2. We examined the ability of these peptides to stimulate G protein activation in human μ-opioid receptor transfected B82 fibroblasts as measured by [ 35 S] GTP γS binding to cell membranes. Both endomorphin-1 and -2 act as partial agonists in this assay system compared with the μ-selective agonist [ d-Ala 2, N-Me-Phe 4, Gly-ol 5]enkephalin (DAMGO). In addition, endomorphins demonstrate efficacy similar to morphine. These findings demonstrate that endomorphin peptides have similar activity at the μ-opioid receptor as morphine and suggest that these peptides have the potential to modulate neuronal activity in vivo.