Phosphorylation of mu-opioid receptors--a putative mechanism of selective uncoupling of receptor--Gi interaction, measured with low-Km GTPase and nucleotide-sensitive agonist binding

H Harada; H Ueda; Y Wada; T Katada; M Ui; M Satoh

doi:10.1016/0304-3940(89)90688-5

Phosphorylation of mu-opioid receptors--a putative mechanism of selective uncoupling of receptor--Gi interaction, measured with low-Km GTPase and nucleotide-sensitive agonist binding

Neurosci Lett. 1989 May 22;100(1-3):221-6. doi: 10.1016/0304-3940(89)90688-5.

Authors

H Harada¹, H Ueda, Y Wada, T Katada, M Ui, M Satoh

Affiliation

¹ Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.

PMID: 2548127
DOI: 10.1016/0304-3940(89)90688-5

Abstract

The mu-opioid receptor agonist stimulation of low-Km GTPase in rat striatal membranes was abolished by islet-activating protein (IAP) treatment, and recovered by Gi reconstitution. When the IAP-treated membranes were phosphorylated with a cAMP-dependent protein kinase, there was no such recovery by Gi. The agonist binding was not affected with respect to Kd, Bmax and sensitivity to guanine nucleotides in the phosphorylated membranes. These findings suggest that phosphorylation of mu-opioid receptors dissociates the agonist change in G-protein activity from the guanine nucleotide-sensitive agonist binding.

MeSH terms

Animals
Corpus Striatum / drug effects
Corpus Striatum / metabolism*
Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
Enkephalins / metabolism
GTP Phosphohydrolases / metabolism*
GTP-Binding Proteins / metabolism*
Male
Phosphoric Monoester Hydrolases / metabolism*
Phosphorylation
Protein Kinases / pharmacology*
Rats
Rats, Inbred Strains
Receptors, Opioid / drug effects
Receptors, Opioid / metabolism*
Receptors, Opioid, mu

Substances

Enkephalins
Receptors, Opioid
Receptors, Opioid, mu
Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
Protein Kinases
Phosphoric Monoester Hydrolases
GTP Phosphohydrolases
GTP-Binding Proteins