Participation of voltage-dependent calcium channels in the regulation of adrenal glomerulosa function by angiotensin II and potassium

Endocrinology. 1986 Jan;118(1):112-8. doi: 10.1210/endo-118-1-112.

Abstract

The stimulation of aldosterone secretion from adrenal glomerulosa cells by angiotensin II (AII), potassium, and ACTH is highly dependent on the extracellular calcium concentration. To evaluate the role of voltage-dependent calcium channels in aldosterone production, we analyzed the actions and binding of calcium channel antagonists in collagenase-dispersed adrenal glomerulosa cells and membrane-rich particles. In rat glomerulosa cells, nifedipine caused dose-dependent inhibition of the aldosterone responses to AII and potassium, with half-maximum inhibitory concentration (IC50) of 100 nM, but had no effect on ACTH or 8-bromo-cAMP stimulated steroidogenesis in adrenal glomerulosa and fasciculata cells. Binding studies with [3H]nitrendipine in adrenal glomerulosa cells revealed a high affinity site with dissociation constant (Kd) of 0.4 +/- 0.1 nM, similar to that described in other tissues but about 100-fold lower than the IC50 for blockade of aldosterone production. However, Scatchard analysis of binding data from three of seven experiments in isolated adrenal glomerulosa cells revealed a low affinity site with Kd of 130 nM, in agreement with the IC50 for the effect of nifedipine on aldosterone production. In rat adrenal particles, nitrendipine-binding sites were located in the adrenal capsule and medulla and were undetectable in the zona fasciculata. Furthermore, there was a close correlation (r = 0.92) between the concentrations of nitrendipine-binding sites and AII receptors in the different zones of the adrenal in rat, dog, and cow, suggesting a functional relationship between AII receptors and calcium channels. These studies have shown a major and selective role of voltage-dependent calcium channels in the control of aldosterone secretion by the major physiological regulators, AII and potassium.

MeSH terms

  • 8-Bromo Cyclic Adenosine Monophosphate / pharmacology
  • Adrenal Glands / drug effects
  • Adrenal Glands / physiology*
  • Adrenocorticotropic Hormone / pharmacology
  • Aldosterone / biosynthesis*
  • Angiotensin II / pharmacology*
  • Animals
  • Binding, Competitive
  • Calcium / metabolism*
  • Calcium / pharmacology
  • Cell Membrane / metabolism
  • Corticosterone / biosynthesis
  • Diltiazem / pharmacology
  • Dose-Response Relationship, Drug
  • Ion Channels / physiology*
  • Male
  • Nifedipine / analogs & derivatives
  • Nifedipine / metabolism
  • Nifedipine / pharmacology
  • Nitrendipine
  • Potassium / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Receptors, Angiotensin / metabolism

Substances

  • Ion Channels
  • Receptors, Angiotensin
  • Angiotensin II
  • 8-Bromo Cyclic Adenosine Monophosphate
  • Aldosterone
  • Adrenocorticotropic Hormone
  • Nitrendipine
  • Diltiazem
  • Nifedipine
  • Potassium
  • Calcium
  • Corticosterone