[3H]nitrendipine binding to adrenal capsular membranes

Area of Science:

• Endocrinology
• Molecular Pharmacology
• Calcium Signaling

Background:

• Aldosterone secretion is regulated by extracellular calcium, mediated by intracellular calcium in zona glomerulosa cells.
• Voltage-dependent calcium channels are implicated in this process, as suggested by studies with verapamil.

Purpose of the Study:

• To investigate the presence and characteristics of [3H]nitrendipine calcium channel binding sites in adrenal capsules.
• To determine the role of these binding sites in the regulation of aldosterone production.

Main Methods:

• Radioligand binding assays using [3H]nitrendipine on adrenal capsules.
• Inhibition studies with various calcium channel antagonists (nitrendipine, nifedipine, verapamil, diltiazem).
• Physiologic studies using collagenase-dispersed adrenal glomerulosa cells to assess steroidogenesis.

Main Results:

• A single class of high-affinity [3H]nitrendipine binding sites was identified in adrenal capsules (KD = 0.26 +/- 0.04 nM, Bmax = 105 +/- 5.7 fmol/mg protein).
• Binding was inhibited by nitrendipine and nifedipine, with less potency by verapamil, and unaffected by diltiazem.
• These binding sites were localized to the adrenal capsule and medulla in rats.
• Nifedipine selectively inhibited angiotensin-II and potassium-stimulated steroidogenesis in glomerulosa cells.

Conclusions:

• The nitrendipine binding site plays a pharmacologic and physiologic role in aldosterone production.
• Voltage-dependent calcium channels are involved in regulating aldosterone secretion.