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Titolo:
mu-opioid receptor and alpha(2)-adrenoceptor agonist stimulation of [S-35]GTP gamma S binding to G-proteins in postmortem brains of opioid addicts
Autore:
Meana, JJ; Gonzalez-Maeso, J; Garcia-Sevilla, JA; Guimon, J;
Indirizzi:
Univ Basque Country, Dept Pharmacol, E-48940 Leioa, Bizkaia, Spain Univ Basque Country Leioa Bizkaia Spain E-48940 940 Leioa, Bizkaia, Spain Univ Geneva, HUG, Hop Belle Idee, Fac Med,Dept Psychiat, CH-1225 Chenebourg, Switzerland Univ Geneva Chenebourg Switzerland CH-1225 -1225 Chenebourg, Switzerland
Titolo Testata:
MOLECULAR PSYCHIATRY
fascicolo: 3, volume: 5, anno: 2000,
pagine: 308 - 315
SICI:
1359-4184(200005)5:3<308:MRAAAS>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
CHRONIC MORPHINE TREATMENT; HUMAN OPIATE ADDICTS; RAT LOCUS-COERULEUS; KINASE-C-ALPHA; CROSS-TOLERANCE; GUANINE-NUCLEOTIDE; ADENYLYL-CYCLASE; HEROIN-ADDICTS; WITHDRAWAL; CLONIDINE;
Keywords:
opioid dependence; human brain; guanosine 5 '-O-(3-thiotriphosphate); mu-opioid receptor; alpha(2)-adrenoceptor; substance-related disorders;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Meana, JJ Univ Basque Country, Dept Pharmacol, E-48940 Leioa, Bizkaia, Spain Univ Basque Country Leioa Bizkaia Spain E-48940 Bizkaia, Spain
Citazione:
J.J. Meana et al., "mu-opioid receptor and alpha(2)-adrenoceptor agonist stimulation of [S-35]GTP gamma S binding to G-proteins in postmortem brains of opioid addicts", MOL PSYCHI, 5(3), 2000, pp. 308-315

Abstract

Repeated opioid administration has been associated in human brain with unaltered density of mu-opioid receptors (agonist radioligand binding sites and immunodetected receptor protein), These receptors are coupled to G(i)/G(o)-proteins, which are increased in brain of heroin addicts. To assess the activity of G-proteins and their coupling to receptors after chronic opioid abuse, [S-35]GTP gamma S binding was quantified in postmortem prefrontal cortices of 15 opioid-dependent subjects and 15 matched controls. The stimulation of [S-35]GTP gamma S binding by the mu-opioid receptor agonist DAMGO or the alpha(2)-adrenoceptor agonist UK14304 was used as a functional measure of the status of the receptor-G-protein coupling, [S-35]GTP gamma S binding basal values were similar in opioid addicts (819 +/- 83 fmol mg(-1) of protein) and controls (918 +/- 106 fmol mg(-1) of protein). In opioid addicts, [S-35]GTP gamma S binding stimulation by DAMGO showed a maximal effect (62 +/- 8%) and a potency (EC50 = 1.09 +/- 0.26 mu M) that did not differ from the maximal effect (60 +/- 12%) and potency (EC50 = 2.01 +/- 0.58 mu M) in controls. In opioid addicts, [S-35]GTP gamma S binding stimulation by UK14304 was not different in maximal effect (28 +/- 3%) from controls (32 +/-8%), but the potency of the agonist was decreased (EC50 = 4.36 +/- 1.81 muM) when compared with controls (EC50 = 0.41 +/- 0.15 mu M). The results provide a direct evidence of an apparent normal functional activity of brain mu-opioid receptors (G(i)/G(o)-protein coupling) during the opioid dependence process in humans. The data also demonstrate a functional uncoupling of alpha(2)-adrenoceptors from G-proteins, which indicates a heterologous desensitization of these receptors. This finding could represent an adaptive mechanism against the decreased noradrenergic activity induced by the chronicpresence of opioid drugs.

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Documento generato il 10/04/20 alle ore 00:16:38