RELATIONSHIP AMONG CONTRACTION, DRUG BINDING AND POSITIVE INOTROPIC ACTION OF DIGOXIN

¹ Department of Pharmacology, Northwestern University Medical School, Chicago, Illinois

Experiments were conducted to determine whether myocardial contraction will enhance binding of digoxin to cardiac receptors. Uptake and retention of H³-digoxin and contractile force measurements were determined in isolated contracting and ``quiescent'' guinea-pig left atria. No difference in concentration of H³-digoxin could be detected between the two washed preparations. When the washed preparations were permitted to contract in drug-free media, again no difference in drug concentration was noted. However, the positive inotropic effect was significantly greater in atria exposed to the drug while contracting, in comparison to quiescent preparations. To determine whether or not a small, differentially bound and contraction-dependent pool of H³-digoxin may still be present in the atria, drug half-life experiments were conducted. Again, contracting and quiescent preparations gave identical drug half-life values of 48 minutes, with only one exponential phase present over a three-hour period. Finally, pharmacologic half-life values were also determined for both types of atrial preparations. Similar values of 45 ± 6 minutes (S.E.) for contracting atria and 44 ± 5 minutes for quiescent atria were obtained. In addition, the pharmacologic half-life values are not significantly different from the drug half-life values. Therefore, present findings indicate that contraction per se does not enhance binding affinity of digitalis glycosides to myocardial receptors.

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