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 [³⁵S]GTPγS binding to cell membranes. Both endomorphin-1 and -2 act as partial agonists in this assay system compared with the μ-selective agonist [D-Ala²,N-Me-Phe⁴, Gly-ol⁵]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.