SPECIFIC G-PROTEIN ACTIVATION AND MU-OPIOID RECEPTOR INTERNALIZATION CAUSED BY MORPHINE, DAMGO AND ENDOMORPHIN-I

Previous studies have shown that the agonist [D-Ala(2), N-Me-Phe(4), G ly-ol(5)]enkephalin (DAMGO) but not morphine induces mu-opioid recepto r internalization [Arden, J.R., Segredo, V., Wang, Z., Lameh, J., Sade e, W., 1995. J. Neurochem. 65, 1636-1645]. In the present study we inv estigated the relationship between internalization of the mu-opioid re ceptor and the specific G proteins activated following treatment with morphine, DAMGO and endomorphin I (Tyr-Pro-Trp-Phe-NH2) (a putative en dogenous mu-opioid receptor agonist) in human embryonic kidney (HEK) c ells. Endomorphin I and DAMGO, but not morphine, caused mu-opioid rece ptor internalization. Morphine, DAMGO and endomorphin I each activated Gi(1) alpha/Gi(2) alpha, Go alpha and Gi(3) alpha to a similar extent , but not Gq alpha/G11 alpha or Gs alpha in HEK membranes. Therefore, the three ligands tested differed in their ability to internalize mu-o pioid receptors even though they were similar in activating individual G proteins. (C) 1998 Elsevier Science B.V.