Site Mutation in the Rat μ-Opioid Receptor Demonstrates the Involvement of Calcium/Calmodulin-Dependent Protein Kinase II in Agonist-Mediated Desensitization
Article first published online: 18 NOV 2002
Journal of Neurochemistry
Volume 69, Issue 4, pages 1767–1770, October 1997
How to Cite
Koch, T., Kroslak, T., Mayer, P., Raulf, E. and Höllt, V. (1997), Site Mutation in the Rat μ-Opioid Receptor Demonstrates the Involvement of Calcium/Calmodulin-Dependent Protein Kinase II in Agonist-Mediated Desensitization. Journal of Neurochemistry, 69: 1767–1770. doi: 10.1046/j.1471-4159.1997.69041767.x
- Issue published online: 18 NOV 2002
- Article first published online: 18 NOV 2002
- Resubmitted manuscript received June 24, 1997; accepted June 24, 1997.
- μ-Opioid receptor;
- Calcium / calmodulin - dependent protein kinase phosphorylation;
- G protein-activated channel;
- Xenopus oocytes
Abstract: The rat μ-opioid receptor (rMOR1), expressed in human embryonic kidney 293 (HEK293) cells, shows a desensitization to the inhibitory effect of the μ agonist DAMGO on adenylate cyclase activity within 4 h of DAMGO preincubation. To investigate the role of calcium/calmodulin-dependent protein kinase II (CaM kinase II) on μ-opioid receptor desensitization, we coexpressed rMOR1 and constitutively active CaM kinase II in HEK293 cells. This coexpression led to a faster time course of agonist-induced desensitization of the μ-opioid receptor. The increase of desensitization could not be observed with a μ-opioid receptor mutant (S261A/S266A) that lacks two putative CaM kinase II phosphorylation sites in the third intracellular loop. In addition, injection of CaM kinase II in Xenopus oocytes led only to desensitization of expressed rMOR1, but not of an S261A/S266A receptor mutant. These results suggest that phosphorylation of Ser261 and Ser266 by CaM kinase II is involved in the desensitization of the μ-opioid receptor.