Specific G protein activation and mu-opioid receptor internalization caused by morphine, DAMGO and endomorphin I

Eur J Pharmacol. 1998 Jan 19;342(1):123-6. doi: 10.1016/s0014-2999(97)01556-2.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analgesics, Opioid / pharmacology*
  • Biotransformation / drug effects
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Enkephalins / pharmacology*
  • GTP-Binding Proteins / drug effects
  • GTP-Binding Proteins / metabolism*
  • Guanosine 5'-O-(3-Thiotriphosphate) / pharmacology
  • Humans
  • Microscopy, Confocal
  • Morphine / pharmacology*
  • Oligopeptides / pharmacology*
  • Receptors, Opioid, mu / agonists
  • Receptors, Opioid, mu / drug effects
  • Receptors, Opioid, mu / metabolism*


  • Analgesics, Opioid
  • Enkephalins
  • Oligopeptides
  • Receptors, Opioid, mu
  • endomorphin 1
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Morphine
  • GTP-Binding Proteins