[3H]nitrendipine binding to adrenal capsular membranes.
The physiologic regulation of aldosterone secretion is dependent on extracellular calcium and appears to be mediated by increases in cytosolic free calcium concentration in the zona glomerulosa cell. A specific role for voltage-dependent calcium channels was suggested by previous studies with the calcium channel antagonist verapamil. We therefore studied the [3H]nitrendipine calcium channel binding site in adrenal capsules. These studies revealed a single class of saturable, high affinity sites with KD = .26 +/- .04 nM and Bmax = 105 +/- 5.7 fmol/mg protein. Specific binding of [3H]nitrendipine was inhibited by calcium channel antagonists with potencies nitrendipine = nifedipine much greater than 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 potassium-stimulated steroidogenesis. These observations suggest both a pharmacologic and physiologic role for the nitrendipine binding site in aldosterone production.
D000313:Adrenal Medulla / Q000378:metabolism*; D000450:Aldosterone / Q000096:biosynthesis; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D004110:Diltiazem / Q000378:metabolism; D007700:Kinetics; D008566:Membranes / Q000378:metabolism; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000378:metabolism; D009568:Nitrendipine; D051381:Rats; D014700:Verapamil / Q000378:metabolism
D000450:Aldosterone; D009568:Nitrendipine; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine