Opioid receptor-coupled G-proteins in rat locus coeruleus membranes: decrease in activity after chronic morphine treatment

Opioid receptor-coupled G-proteins in rat locus coeruleus membranes: decrease in activity after... The nucleus locus coeruleus is involved in the expression of opiate physical dependence and withdrawal, and has been characterized extensively with regard to chronic morphine-induced alterations in biochemical and electrophysiological responses. In the present study, the effects of chronic morphine treatment on opioid receptor-coupled G-protein activity was investigated in membranes from rat locus coeruleus. Opioid agonists stimulated low K m GTPase activity with pharmacology consistent with mu receptors. Chronic morphine treatment resulted in decreases in both basal and opioid-stimulated low K m GTPase activity, with no change in the percent stimulation by agonist. The decrease in low K m GTPase activity appeared to be due to a decrease in the V max of the enzyme, with no change in the K m for GTP hydrolysis. These results were confirmed by assays of basal and opioid receptor-stimulated ( 35 S)GTP γ S binding in the presence of excess GDP. Thus, chronic morphine treatment apparently decreased inhibitory G-protein activity in the locus coeruleus without producing any detectable desensitization. These results suggest a potential adaptation at the receptor/transducer level which may contribute to other biochemical changes produced in the locus coeruleus by chronic morphine treatment. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Brain Research Elsevier

Opioid receptor-coupled G-proteins in rat locus coeruleus membranes: decrease in activity after chronic morphine treatment

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Publisher
Elsevier
Copyright
Copyright © 1997 Elsevier Science B.V.
ISSN
0006-8993
D.O.I.
10.1016/S0006-8993(96)01125-0
Publisher site
See Article on Publisher Site

Abstract

The nucleus locus coeruleus is involved in the expression of opiate physical dependence and withdrawal, and has been characterized extensively with regard to chronic morphine-induced alterations in biochemical and electrophysiological responses. In the present study, the effects of chronic morphine treatment on opioid receptor-coupled G-protein activity was investigated in membranes from rat locus coeruleus. Opioid agonists stimulated low K m GTPase activity with pharmacology consistent with mu receptors. Chronic morphine treatment resulted in decreases in both basal and opioid-stimulated low K m GTPase activity, with no change in the percent stimulation by agonist. The decrease in low K m GTPase activity appeared to be due to a decrease in the V max of the enzyme, with no change in the K m for GTP hydrolysis. These results were confirmed by assays of basal and opioid receptor-stimulated ( 35 S)GTP γ S binding in the presence of excess GDP. Thus, chronic morphine treatment apparently decreased inhibitory G-protein activity in the locus coeruleus without producing any detectable desensitization. These results suggest a potential adaptation at the receptor/transducer level which may contribute to other biochemical changes produced in the locus coeruleus by chronic morphine treatment.

Journal

Brain ResearchElsevier

Published: Jan 23, 1997

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