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Titolo:
Effect of S20787, a novel Cl--HCO3- exchange inhibitor, on intracellular pH regulation in guinea pig ventricular myocytes
Autore:
Loh, SH; Tsai, CS; Lin, CI; Jin, JS; Vaughan-Jones, RD;
Indirizzi:
Natl Def Med Ctr, Dept Pharmacol, Taipei 100, Taiwan Natl Def Med Ctr Taipei Taiwan 100 r, Dept Pharmacol, Taipei 100, Taiwan Natl Def Med Ctr, Dept Cardiovasc Surg, Taipei 100, Taiwan Natl Def Med Ctr Taipei Taiwan 100 t Cardiovasc Surg, Taipei 100, Taiwan Natl Def Med Ctr, Dept Physiol, Taipei 100, Taiwan Natl Def Med Ctr Taipei Taiwan 100 Ctr, Dept Physiol, Taipei 100, Taiwan Univ Oxford, Physiol Lab, Oxford OX1 3PT, England Univ Oxford Oxford England OX1 3PT Physiol Lab, Oxford OX1 3PT, England
Titolo Testata:
JOURNAL OF BIOMEDICAL SCIENCE
fascicolo: 5, volume: 8, anno: 2001,
pagine: 395 - 405
SICI:
1021-7770(200109)8:5<395:EOSANC>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
CARDIAC ISCHEMIA; CELLS; RAT; RECOVERY; MECHANISMS; ALKALOSIS; HOE-694; PH(I); HEART;
Keywords:
S20787; anion exchange; intracellular pH; cardiac myocytes; Na+-H+ exchange; Na+-HCO3- co-transport; Cl--HCO3- exchange; Cl--OH- exchange; monocarboxylic acid transporter;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
22
Recensione:
Indirizzi per estratti:
Indirizzo: Loh, SH Natl Def Med Ctr, Dept Pharmacol, Neihu POB 90048-504, Taipei 100,Taiwan Natl Def Med Ctr Neihu POB 90048-504 Taipei Taiwan 100 00, Taiwan
Citazione:
S.H. Loh et al., "Effect of S20787, a novel Cl--HCO3- exchange inhibitor, on intracellular pH regulation in guinea pig ventricular myocytes", J BIOMED SC, 8(5), 2001, pp. 395-405

Abstract

S20787 has recently been proposed to be a selective Cl--HCO3- anion exchange (AE) inhibitor in rat cardiomyocytes. The AE transporter mediates sarcolemmal acid influx but is only one part of the cardiac cell's dual acid loading mechanism, the other part being a sarcolemmal Cl--OH- exchanger (CHE). We have therefore (1) investigated the differential effects of S20787 on the AE and CHE transporters in isolated guinea pig ventricular myocytes and (2) re-examined the influence of the drug on other sarcolemmal acid transporters by monitoring its effect on intracellular pH (pH(i)) recovery from alkali or acid loads. The pHi was measured using microspectrofluorimetry (carboxy-SNARF-1). The results indicate that CHE activity was unaffected by the drug (1-20 muM), whereas up to 78% of AE activity was blocked (K-i = 3.9 muM). Thus, S20787 targets only the AE component of the dual acid influx system. Activities of other acid-transporting carriers, such as Na+-H+ exchange, Na+-HCO3- cotransport and the monocarboxylic acid transporter, were unaffected by the drug. The inhibitory efficacy of S20787 for AE in guinea pig cardiomyocytes appears to be considerably higher (approximately 78%) than proposed previously for rat cardiomyocytes (50%). This is most likely because, in both cells, a significant fraction (20-30%) of acid influx is mediatedthrough the S20787-insensitive CHE transporter. Previous studies made no allowance for the CHE component, which would result in an underestimation. S20787 is thus a highly selective AE inhibitor which may be useful as an experimental tool and a potential cardiac protective agent in the heart. Copyright (C) 2001 National Science Council, ROC and S. Karger AG, Basel.

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Documento generato il 25/02/20 alle ore 08:03:44