- 作者: Shih-Hurng loh Chien-Sung Tsai Cheng-I Lin Jong-Shiaw Jin Richard D. Vaughan-Jones
- 作者服務機構: departments of Pharmacology, Cardiovascular Surgery and Physiology, National Defense Medical Center. Taipei, Taiwan, ROC; University Laboratory of Physiology, University of Oxford, Oxford, UK
- 中文摘要: --
- 英文摘要: S20787 has recently been proposed to be a selective CI--HCO anion exchange (AE) inhibitor in rat cardiomyo-cytes. The AE transporter mediates sarcolemmal acidinflux but is only one part of the cardiac cell's dual acidloading mechanism, the other part being a sarcolemmalCI -OH exchanger (CHE). We have therefore (1) investi-gated the differential effects of S20787 on the AE andCHE transporters in isolated guinea pig ventricular myo-cytes and (2) re-examined the influence of the drug onother sarcolemmal acid transporters by monitoring itseffect on intracellular pH (pH ) recovery from alkali oracid loads. The pH was measured using microspectro-fluorimetry (carboxy-SNARF-1). The results indicate thatCHE activity was unaffected by the drug (1-20 M),whereas up to 78% of AE activity was blocked (K =3.9 M). Thus, S20787 targets only the AE component ofthe dual acid influx system. Activities of other acid-trans-porting carriers, such as Na -H exchange, Na -HCO co-transport and the monocarboxylic acid transporter, wereunaffected by the drug. The inhibitory efficacy of S20787for AE in guinea pig cardiomyocytes appears to be con-siderably higher (approximately 78%) than proposedpreviously for rat cardiomyocytes (50%). This is mostlikely because, in both cells, a significant fraction (20-30%) of acid influx is mediated through the S20787-insensitive CHE transporter. Previous studies made noallowance for the CHE component, which would result inan underestimation. S20787 is thus a highly selective AEinhibitor which may be useful as an experimental tooland a potential cardiac protective agent in the heart.
- 中文關鍵字: --
- 英文關鍵字: S20787. Anion exchange. Intacellular pH. Cardiac myocytes. Na-H exchange. co-transport. Ci-HCO-exchange, CI-OH- exchange. Monocarboxylic acid transporter