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Titolo:
Alterations in detergent solubility of heterotrimeric G proteins after chronic activation of G(i/o)-coupled receptors: Changes in detergent solubility are in correlation with onset of adenylyl cyclase superactivation
Autore:
Bayewitch, ML; Nevo, I; Avidor-Reiss, T; Levy, R; Simonds, WF; Vogel, Z;
Indirizzi:
Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel Weizmann Inst Sci Rehovot Israel IL-76100 biol, IL-76100 Rehovot, Israel NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA NIDDKD Bethesda MD USA 20892 etab Dis Branch, NIH, Bethesda, MD 20892 USA
Titolo Testata:
MOLECULAR PHARMACOLOGY
fascicolo: 4, volume: 57, anno: 2000,
pagine: 820 - 825
SICI:
0026-895X(200004)57:4<820:AIDSOH>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
BETA-GAMMA-SUBUNITS; CHRONIC OPIOID TREATMENT; GTP-BINDING PROTEINS; INHIBITORY RECEPTORS; MODULATION; DEPENDENCE; REDUCTION; EXPOSURE; MEMBRANE; ISOFORM;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Vogel, Z Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel Weizmann Inst Sci Rehovot Israel IL-76100 76100 Rehovot, Israel
Citazione:
M.L. Bayewitch et al., "Alterations in detergent solubility of heterotrimeric G proteins after chronic activation of G(i/o)-coupled receptors: Changes in detergent solubility are in correlation with onset of adenylyl cyclase superactivation", MOLEC PHARM, 57(4), 2000, pp. 820-825

Abstract

Prolonged G(i/o) protein-coupled receptor activation has been shown to lead to receptor internalization and receptor desensitization. In addition, itis well established that although acute activation of these receptors leads to inhibition of adenylyl cyclase (AC), long-term activation results in increased AC activity (especially evident on removal of the inhibitory agonist), a phenomenon defined as AC superactivation or sensitization. Herein, we show that chronic exposure to agonists of G(i)-coupled receptors also leads to a decrease in cholate detergent solubility of G protein subunits, andthat antagonist treatment after such chronic agonist exposure leads to a time-dependent reversal of the cholate insolubility. With Chinese hamster ovary and COS cells transfected with several G(i/o)-coupled receptors (i.e., mu- and kappa-opioid, and m(4)-muscarinic), we observed that although no overall change occurred in total content of G(alpha i)- and beta(1)-subunits,chronic agonist treatment led to a marked reduction in the ability of 1% cholate to solubilize G(beta gamma) as well as G(alpha i). This solubility shift is exclusively observed with G(alpha i), and was not seen with G(alphas). The disappearance and reappearance of G(alpha i) and G(beta gamma) subunits from and to the detergent-soluble fractions occur with similar time courses as observed for the onset and disappearance of AC superactivation. Lastly, pertussis toxin, which blocks acute and chronic agonist-induced AC inhibition and superactivation, also blocks the shift in detergent solubility. These results suggest a correlation between the solubility shift of the heterotrimeric G(i) protein and the generation of AC superactivation.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/07/20 alle ore 23:50:21