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Titolo:
Monovalent anions differentially modulate coupling of the beta(2)-adrenoceptor to G(s alpha) splice variants
Autore:
Seifert, R;
Indirizzi:
Univ Kansas, Dept Pharmacol & Toxicol, Lawrence, KS 66045 USA Univ KansasLawrence KS USA 66045 macol & Toxicol, Lawrence, KS 66045 USA Stanford Univ, Howard Hughes Med Inst, Beckman Ctr, Stanford, CA 94305 USAStanford Univ Stanford CA USA 94305 , Beckman Ctr, Stanford, CA 94305 USA
Titolo Testata:
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
fascicolo: 2, volume: 298, anno: 2001,
pagine: 840 - 847
SICI:
0022-3565(200108)298:2<840:MADMCO>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
GTP-BINDING PROTEINS; REGULATORY PROTEINS; ALPHA-SUBUNIT; CONSTITUTIVE ACTIVITY; RECEPTOR ACTIVATION; MOLECULAR ANALYSIS; CARDIAC MEMBRANES; OPIOID RECEPTORS; GS-ALPHA; ANTAGONISTS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
33
Recensione:
Indirizzi per estratti:
Indirizzo: Seifert, R Univ Kansas, Dept Pharmacol & Toxicol, 5064 Malott Hall, Lawrence, KS 66045 USA Univ Kansas 5064 Malott Hall Lawrence KS USA 66045 KS 66045 USA
Citazione:
R. Seifert, "Monovalent anions differentially modulate coupling of the beta(2)-adrenoceptor to G(s alpha) splice variants", J PHARM EXP, 298(2), 2001, pp. 840-847

Abstract

The beta (2)-adrenoceptor (beta (2)AR) fused to the long splice variant ofG(s alpha) (G(s alphaL)), but not the beta (2)AR fused to the short splicevariant of G(s alpha) (G(s alphaS)) shows the hallmarks of high constitutive activity, i.e., strong activation of adenylyl cyclase (AC) by GTP and strong inhibition of AC by inverse agonist. These coupling differences are the result of differences in GDP affinity of G(s alpha) splice variants. The aim of this study was to identify experimental variables that differentially affect beta (2)AR coupling to G(s alphaS) and G(s alphaL). NaCl substantially reduced agonist-independent AC activation by GTP and inverse agonist inhibition and enhanced agonist stimulation of AC in Sf9 insect cell membranes expressing the beta (2)AR-G(S alphaL) fusion protein. Salts reduced inverse agonist inhibition and increased agonist stimulation of AC in the orderof efficiency Nal similar to Kl > NaBr similar to KBr > NaCl similar to LiCl similar to KCl similar to RbCI similar to CsCl similar to choline chloride, indicating that monovalent anions determine salt effects. Salts inhibited guanosine 5'-O-(3-thiotriphosphate)-mediated AC activation by G(s alphaL) without beta (2)AR in the order of efficiency Nal > NaBr > NaCl. NaCl enhanced the affinity of G(s alphaL) for GDP. Salts had much smaller effects on beta(2)AR ligand regulation of AC in membranes expressing beta (2)AR-G(s alphaS) than in membranes expressing beta (2)AR-G(s alphaL). These data areexplained by a model in which anions increase the GDP affinity of G(s alphaL) more efficiently than the GDP affinity of G(s alphaS), and, thereby, decrease the efficiency of the agonist-free beta (2)AR and increase the efficiency of the agonist-occupied beta (2)AR at promoting GDP dissociation fromG(s alphaL). Thus, monovalent anions differentially regulate beta (2)AR-coupling to G(s alphaS) and G(s alphaL).

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 02:41:00