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Tritium labeled nitrendipine binding to adrenal capsular membranes


, : Tritium labeled nitrendipine binding to adrenal capsular membranes. Life Sciences 35(8): 905-910

The physiological regulation of aldosterone secretion is dependent on extracellular Ca, and appears to be mediated by increases in cytosolic free Ca concentration in the zona glomerulosa cell. A specific role for voltage-dependent Ca channels was suggested by previous studies with the Ca channel antagonist verapamil. The [3H]nitrendipine Ca channel binding site was studied in [rat] adrenal capsules. These studies revealed a single class of saturable, high affinity sites with Kd = 0.26 .+-. 0.04 nM and Bmax = 105 .+-. 5.7 fmol/mg protein. Specific binding of [3H] nitrendipine was inhibited by Ca channel antagonists with potencies nitrendipine = nifedipine .mchgt. verapamil, while diltiazem had no inhibitory effect. In the rat, binding sites for [3H]nitrendipine were located in the adrenal capsule and medulla and were undetectable in the zona fasciculata. Physiologic studies with collagenase-dispersed adrenal glomerulosa cells demonstrated that nifedipine selectively inhibited angiotensin-II and K-stimulated steroidogenesis. These observations suggest both a pharmacologic and physiologic role for the nitrendipine binding site in aldosterone production.

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