作者: P. K. Siegl , E. J. Cragoe , M. J. Trumble , G. J. Kaczorowski
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摘要: Abstract Na+/Ca2+ exchange is inhibited in both guinea pig cardiac membrane vesicles and papillary muscles a concentration-dependent fashion by several analogs of the pyrazine diuretic amiloride. Structure/activity studies based on transport measurements prepared from left ventricle indicate that hydrophobic substitutions at terminal nitrogen atom guanidinium moiety amiloride improved inhibitory potency almost 100-fold over parent compound. 3',4'- Dichlorobenzamil ( DCB ) one most active inhibitors (IC50 = 17 microM). In electrically stimulated isolated heart, 10-40 microM decreases contractile force. At 100 inhibitor, diastolic tension significantly increased. The positive inotropic responses to veratridine ouabain are 20 40 . Since these interventions were consequence increased intracellular Na+ concentration, data an inhibitor Na+-dependent Ca2+ influx intact tissue. Interpretation mechanical elicited paired pulses suggests but not release sarcoplasmic reticulum. obtained with concentrations Na+/Ca2+ suggest significant amount can enter cell via under normal conditions this system may be important source supplying reticulum heart. Moreover, function as potent effect caused concentration.