Chronic morphine administration increases beta-adrenergic receptor kinase (beta ARK) levels in the rat locus coeruleus.
Based on the established role of beta-adrenergic receptor kinase (beta ARK) and beta-arrestin in the desensitization of several G protein-coupled receptors, we investigated the effect of chronic morphine administration on beta ARK and beta-arrestin levels in selected brain areas. Levels of beta ARK were measured by blot immunolabeling analysis using antibodies specific for two known forms of beta ARK, i.e., beta ARK1 and beta ARK2. It was found that chronic morphine treatment produced an approximately 35% increase in levels of beta ARK1 immunoreactivity in the locus coeruleus, but not in several other brain regions studied. In contrast, chronic morphine treatment failed to alter levels of beta ARK2 immunoreactivity in any of the brain regions studied. Levels of beta-arrestin immunoreactivity, measured using an antiserum that recognizes two major forms of this protein in brain, were also found to increase (by approximately 20%) in the locus coeruleus. It is proposed that chronic morphine regulation of beta ARK1 and beta-arrestin levels may contribute to opioid-receptor tolerance that is known to occur in this brain region.
Terwilliger
R Z
RZ
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06508.
Ortiz
J
J
Guitart
X
X
Nestler
E J
EJ
D000818:Animals; D000941:Antigens / Q000032:analysis / Q000378:metabolism; D019390:Arrestins; D017868:Cyclic AMP-Dependent Protein Kinases / Q000032:analysis* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005136:Eye Proteins / Q000032:analysis / Q000378:metabolism; D007150:Immunohistochemistry; D008125:Locus Coeruleus / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051552:beta-Adrenergic Receptor Kinases; D000071557:beta-Arrestins
D000941:Antigens; D019390:Arrestins; D005136:Eye Proteins; D000071557:beta-Arrestins; D009020:Morphine; D017868:Cyclic AMP-Dependent Protein Kinases; D051552:beta-Adrenergic Receptor Kinases