Specific G protein activation and mu-opioid receptor internalization caused by morphine, DAMGO and endomorphin I.
Previous studies have shown that the agonist [D-Ala2, N-Me-Phe4, Gly-ol5]enkephalin (DAMGO) but not morphine induces mu-opioid receptor internalization [Arden, J.R., Segredo, V., Wang, Z., Lameh, J., Sadee, W., 1995. J. Neurochem. 65, 1636-1645]. In the present study we investigated the relationship between internalization of the mu-opioid receptor and the specific G proteins activated following treatment with morphine, DAMGO and endomorphin I (Tyr-Pro-Trp-Phe-NH2) (a putative endogenous mu-opioid receptor agonist) in human embryonic kidney (HEK) cells. Endomorphin I and DAMGO, but not morphine, caused mu-opioid receptor internalization. Morphine, DAMGO and endomorphin I each activated Gi1 alpha/Gi2 alpha, Go alpha and Gi3 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-opioid receptors even though they were similar in activating individual G proteins.
Burford
N T
NT
Department of Biopharmaceutical Sciences and Pharmaceutical Chemistry, University of California, San Francisco 94143-0446, USA. ntburf@itsa.ucsf.edu
Tolbert
L M
LM
Sadee
W
W
D000701:Analgesics, Opioid / Q000494:pharmacology*; D001711:Biotransformation / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006801:Humans; D018613:Microscopy, Confocal; D009020:Morphine / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000187:drug effects / Q000378:metabolism*
D000701:Analgesics, Opioid; D004745:Enkephalins; D009842:Oligopeptides; D017450:Receptors, Opioid, mu; C105293:endomorphin 1; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D009020:Morphine; D019204:GTP-Binding Proteins