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Titolo:
CARDIAC DESENSITIZATION TO ADENOSINE-ANALOGS AFTER PROLONGED R-PIA INFUSION IN-VIVO
Autore:
LEE HT; THOMPSON CI; HERNANDEZ A; LEWY JL; BELLONI FL;
Indirizzi:
NEW YORK MED COLL,DEPT PHYSIOL,BASIC SCI BLDG VALHALLA NY 10595 NEW YORK MED COLL,DEPT PHYSIOL,BASIC SCI BLDG VALHALLA NY 10595
Titolo Testata:
The American journal of physiology
fascicolo: 6, volume: 265, anno: 1993,
parte:, 2
pagine: 80001916 - 80001927
SICI:
0002-9513(1993)265:6<80001916:CDTAAP>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
ADENYLATE CYCLASE SYSTEM; PERTUSSIS TOXIN; POTASSIUM CONDUCTANCE; RECEPTOR AGONIST; DOWN-REGULATION; HEART-CELLS; GUINEA-PIG; G-PROTEINS; RAT-BRAIN; BINDING;
Keywords:
CARDIAC ADENOSINE RECEPTORS; DOWN-REGULATION; R-(-)-N6-(2-PHENYLISOPROPYL)ADENOSINE; 8-CYCLOPENTYL-1,3-DIPROPYLXAN-THINE; RECEPTOR BINDING; WESTERN BLOTTING; INHIBITORY AND STIMULATORY GUANINE NUCLEOTIDE-BINDINGPROTEINS; ATRIAL MUSCLE; N6-CYCLOPENTYLADENOSINE; 5'-N-ETHYLCARBOXAMIDOADENOSINE; 2-CHLOROADENOSINE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
36
Recensione:
Indirizzi per estratti:
Citazione:
H.T. Lee et al., "CARDIAC DESENSITIZATION TO ADENOSINE-ANALOGS AFTER PROLONGED R-PIA INFUSION IN-VIVO", The American journal of physiology, 265(6), 1993, pp. 80001916-80001927

Abstract

To determine the effects of chronic in vivo stimulation of adenosine receptors, R-(-)-N6-(2-phenylisopropyl)adenosine (R-PIA), a selective A1 receptor agonist, was administered to rats as a continuous 7-day infusion (200 nmol/h). Inotropic and chronotropic responses of isolated atria to adenosine receptor agonists were markedly desensitized compared with the responses of atria from ap-matched control animals. Carbachol's negative chronotropic effect was also attenuated, indicating a heterologous mode of desensitization. Antagonist radioligand binding-assays indicated a 52% reduction in A1 adenosine receptor maximum binding, and competition binding assays revealed a significant loss of G protein-coupled high-affinity A1 receptors in atria from R-PIA-treated rats. Inhibitory G proteins (G(i)) were significantly reduced, as quantified by immunoblot analysis, with no change in the amount of stimulatory G proteins. Ventricular membranes from R-PIA rats showed loss of G(i) and uncoupling of A1 receptors, without a significant change in A1 receptor density. Thus chronic R-PIA infusion desensitized rat atrial muscle to the effects of adenosine receptor agonists via several regulatory adaptations, including downregulation of A1 adenosine receptors,uncoupling of A1 receptors from their associated G proteins, and lossof G(i) proteins.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/07/20 alle ore 20:17:21