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Titolo:
RGS9 proteins facilitate acute tolerance to mu-opioid effects
Autore:
Garzon, J; Rodriguez-Diaz, M; Lopez-Fando, A; Sanchez-Blazquez, P;
Indirizzi:
CSIC, Inst Neurobiol Santiago Ramon & Cajal, E-28002 Madrid, Spain CSIC Madrid Spain E-28002 Santiago Ramon & Cajal, E-28002 Madrid, Spain
Titolo Testata:
EUROPEAN JOURNAL OF NEUROSCIENCE
fascicolo: 4, volume: 13, anno: 2001,
pagine: 801 - 811
SICI:
0953-816X(200102)13:4<801:RPFATT>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
ANTISENSE OLIGODEOXYNUCLEOTIDES; PERIAQUEDUCTAL GRAY; MORPHINE-DEPENDENCE; SIGNALING PROTEINS; RAT; RECEPTOR; DESENSITIZATION; REGULATORS; BRAIN; CHANNELS;
Keywords:
I-125-Tyr(27); human beta-endorphin; analgesia; antinociception; antisense technology; G-proteins; mouse; receptor desensitization; regulator of G-protein signalling;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
44
Recensione:
Indirizzi per estratti:
Indirizzo: Garzon, J CSIC, Inst Neurobiol Santiago Ramon & Cajal, Ave Doctor Arce 37,E-28002 Madrid, Spain CSIC Ave Doctor Arce 37 Madrid Spain E-28002 8002 Madrid, Spain
Citazione:
J. Garzon et al., "RGS9 proteins facilitate acute tolerance to mu-opioid effects", EUR J NEURO, 13(4), 2001, pp. 801-811

Abstract

This paper reports that regulators of G-protein signalling (RGS) proteins modulate the timing and amplitude of opioid signals by a push-pull mechanism. This is achieved without noticeable changes in the binding properties ofopioids, e.g. beta -endorphin to mu-opioid receptors. The expression of RGS proteins was reduced by blocking their mRNA with antisense oligodeoxynucleotides (ODN). Knock down of RGS2 or RGS3 diminished morphine and beta -endorphin analgesia, whereas that of RGS9 or RGS12 enhanced this activity. In mice with impaired RGS9, but not impaired RGS2, the potency and, in particular, the duration of opioid antinociception increased. Further, the animalsdid not exhibit acute tolerance generated by a single and efficacious doseof morphine, nor did they develop tolerance after a daily i.c.v. injectionof the opioid for 4 days. In a model of sustained morphine treatment, the impairment of RGS9 proteins facilitated increases in the response to the delivered opioid. This was only effective for 2-3 h after the subcutaneous implantation of an oily morphine pellet; later, tolerance developed. To reduce the impact of the chronic morphine acting on opioid receptors, other RGS proteins presumably substitute the GTPase-activating function of RGS9 on morphine-activated G alpha -GTP subunits. The desensitization of mu-opioid receptors appears to be a cell membrane-limited process facilitated by RGS9'ssequestering of agonist-segregated G alpha subunits.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 10/07/20 alle ore 17:51:34