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Titolo:
MU-OPIOID RECEPTOR DOWN-REGULATION AND CAMP-DEPENDENT PROTEIN-KINASE PHOSPHORYLATION IN A MOUSE MODEL OF CHRONIC MORPHINE-TOLERANCE
Autore:
BERNSTEIN MA; WELCH SP;
Indirizzi:
VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PHARMACOL & TOXICOL,BOX 980613,MCV STN RICHMOND VA 23298 VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PHARMACOL & TOXICOLRICHMOND VA 23298
Titolo Testata:
Molecular brain research
fascicolo: 2, volume: 55, anno: 1998,
pagine: 237 - 242
SICI:
0169-328X(1998)55:2<237:MRDACP>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
RAT LOCUS-COERULEUS; ADENYLYL-CYCLASE; SPINAL-CORD; BRAIN; DESENSITIZATION; BINDING; MICE; MEMBRANES; NALOXONE; AGONISTS;
Keywords:
MORPHINE; TOLERANCE; PROTEIN KINASE A; MU-OPIOID RECEPTOR; ANTINOCICEPTION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
40
Recensione:
Indirizzi per estratti:
Citazione:
M.A. Bernstein e S.P. Welch, "MU-OPIOID RECEPTOR DOWN-REGULATION AND CAMP-DEPENDENT PROTEIN-KINASE PHOSPHORYLATION IN A MOUSE MODEL OF CHRONIC MORPHINE-TOLERANCE", Molecular brain research, 55(2), 1998, pp. 237-242

Abstract

Results of radioligand binding and transfected receptor studies indicate that mu-receptor down-regulation and phosphorylation may be critical to the expression of morphine tolerance. In this study, an animal model of morphine tolerance was used to correlate antinociception with changes in receptor number and phosphorylation state. mu-Opioid receptor protein was quantitated by Western immunoassay of brainstem tissue from morphine-treated mice. Degree of receptor phosphorylation was assessed using immunoprecipitation (IP) of the receptor followed by back-phosphorylation. Acutely administered morphine produced no changes in mu-receptor quantity. Chronic morphine administration resulted in a 50% reduction in receptor protein quantity over placebo-treated samples. Back-phosphorylation experiments showed a drop in cAMP-dependent protein kinase A (PKA)-induced receptor phosphorylation shortly after acute morphine administration, followed by a naloxone-reversible increase in phosphorylation of the receptor that correlated with the onset of antinociception. Chronic morphine administration resulted in a decreasein PKA-induced phosphorylation of the mu-receptor. Since it has been shown that PKA activity is enhanced in the brains of morphine-tolerantmice, this decrease in mu-receptor phosphorylation suggests that the mu-receptor may be structurally or conformationally altered in the morphine-tolerant state. (C) 1998 Elsevier Science B.V.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/03/20 alle ore 17:50:19