Significance of skeletal muscle digitalis receptors for [3H]ouabain distribution in the guinea pig

K. Kjeldsen, A. Norgaard, O. Hansen, T. Clausen

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    The importance of specific digitalis glycoside binding sites in skeletal muscle for the digitalis glycoside distribution in the guinea pig was evaluated using [3H]ouabain and [3H]digoxin binding assays. Measurements of [3H]ouabain binding capacity (EO(max)) in gastrocnemius and heart muscles in vitro gave values of 474 ± 15 and 1,092 ± 39 pmol/g wet wt., respectively, in 4-week-old guinea pigs. Hence the total amount of [3H]ouabain binding sites in skeletal muscle and the heart was around 42,700 and 1,200 pmol, respectively. The apparent dissociation constants (K(d)) for ouabain receptor interaction was 0.7 x 10-7 and 1.5 x 10-7 M for skeletal muscle and heart, respectively. Comparison of [3H]ouabain and [3H]digoxin binding revealed that these drugs are competitive. From birth to maturity the concentration of [3H]ouabain binding sites in guinea pigs decreased from 803 ± 58 to 304 ± 28 pmol/g wet wt. in gastrocenmius muscle and from 1,458 ± 31 to 1,079 ± 19 pmol/g wet wt. in the heart. After i.p. injection, measurements of the distribution of [3H]ouabain in plasma, skeletal muscle and the heart showed an almost equal relative specific occupancy of digitalis glycoside receptors in skeletal muscle and the heart: When 10% of the digitalis receptors in the heart were occupied by [3H]ouabain, 13% of those in the skeletal muscles were occupied. It was calculated that 1 hr after the i.p. administration of [3H]ouabain the amount of [3H]ouabain specifically bound to the skeletal muscles and the heart corresponded to 5 times and 1/10 the amount available in the extracellular pool, respectively. Taken together the observations emphasize the importance of the skeletal muscle digitalis glycoside receptors as a major pool for the distribution of cardiac glycosides.

    Sider (fra-til)720-727
    Antal sider8
    TidsskriftJournal of Pharmacology and Experimental Therapeutics
    Udgave nummer3
    StatusUdgivet - 1 jan. 1985


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