TY - JOUR T1 - FURTHER STUDIES ON THE CORRELATION BETWEEN THE INOTROPIC ACTION OF OUABAIN AND ITS INTERACTION WITH THE Na<sup>+</sup>, K<sup>+</sup>-ADENOSINE TRIPHOSPHATASE: ISOLATED PERFUSED RABBIT AND CAT HEARTS JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 119 LP - 127 VL - 191 IS - 1 AU - Arnold Schwartz AU - Julius C. Allen AU - W. Barry Van Winkle AU - Ronald Munson Y1 - 1974/10/01 UR - http://jpet.aspetjournals.org/content/191/1/119.abstract N2 - Ouabain-induced increases in contractility were measured on isolated perfused cat and rabbit hearts. At peak inotropism, Na+, K+-adenosine triphosphatase (Na+, K+-ATPase) of cat heart was inhibited compared to control, while at peak inotropism, rabbit heart Na+, K+-ATPase remained at control levels. Infusion and isolation studies using 3H-ouabain indicated that even though 3H-ouabain was present in both rabbit and cat myocardia at peak inotropism, most of the drug dissociated from the rabbit heart enzyme during isolation but remained bound to the cat heart enzyme. Studies also indicated that the inotropic effect disappeared much more readily from rabbit hearts than cat hearts after washing. In the latter case, a return to control level of contractility was coincident with a return to control levels of Na+,K+-ATPase activity. Such studies were not possible with rabbit Na+, K+-ATPase since enzyme activity from inotropic hearts was the same as control activity due to drug washoff during isolation. In vitro binding studies of 3H-ouabain to both cat and rabbit cardiac Na+, K+-ATPase indicated that the stability of the drug-enzyme complex was much higher with cat enzyme than rabbit, consistent with both pharmacologic washout data and drug dissociation during Na+,K+,-ATPase preparation. Such studies suggest that species sensitive to cardiac glycosides should be used to correlate pharmacologic with biochemical effects of certain cardiac glycosides. © 1974 by The Williams &amp; Wilkins Company ER -