Local production and action of adrenomedullin in the rat adrenal zona glomerulosa

This study was designed to investigate the synthesis and action of adrenomedullin in the rat adrenal gland. The results obtained from in situ hybridization and immunocytochemical studies suggest that adrenomedullin is synthesized not only in the medulla, but also within the zona glomerulosa of the rat adrenal cortex. Findings from in situ hybridization and binding studies also suggested that specific adrenomedullin receptors are expressed in the zona glomerulosa, and that low levels are present in the inner zones of the cortex. The Kd of the zona glomerulosa adrenomedullin receptor (5.5 nmol/l) suggests that it may respond to locally produced adrenomedullin rather than circulating concentrations of the peptide, which are in a lower range. It was found that adrenomedullin acted on zona glomerulosa cells in vitro to stimulate aldosterone release and cAMP formation, but in this tissue did not stimulate inositol phosphate turnover. The effect of adrenomedullin on aldosterone secretion was significantly attenuated by a protein kinase A inhibitor, suggesting that cAMP mediates the effects of adrenomedullin on aldosterone secretion. Adrenomedullin did not significantly affect the response of zona glomerulosa cells to stimulation by either ACTH or angiotensin II. Adrenomedullin did not affect the release of catecholamines, either adrenaline or noradrenaline, by intact adrenal capsular tissue. These data suggest that both adrenomedullin and its specific receptor are expressed in the rat adrenal zona glomerulosa, leading to the hypothesis that adrenomedullin may have an autocrine/paracrine role in the regulation of the rat adrenal zona glomerulosa.

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Effect of the endothelins on aldosterone secretion by rat zona glomerulosa cells In vitro

The Journal of Steroid Biochemistry and Molecular Biology ◽

10.1016/0960-0760(91)90213-o ◽

1991 ◽

Vol 40 (1-3) ◽

pp. 437-439 ◽

Cited By ~ 23

Author(s):

J.P. Hinson ◽

S. Kapas ◽

R. Teja ◽

G.P. Vinson

Keyword(s):

Zona Glomerulosa ◽

Aldosterone Secretion ◽

Glomerulosa Cells ◽

Zona Glomerulosa Cells

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α1H T-type Ca2+ channel is the predominant subtype expressed in bovine and rat zona glomerulosa

AJP Cell Physiology ◽

10.1152/ajpcell.2001.280.2.c265 ◽

2001 ◽

Vol 280 (2) ◽

pp. C265-C272 ◽

Cited By ~ 50

Author(s):

Andrew D. Schrier ◽

Hongge Wang ◽

Edmund M. Talley ◽

Edward Perez-Reyes ◽

Paula Q. Barrett

Keyword(s):

Low Voltage ◽

Zona Glomerulosa ◽

Zona Fasciculata ◽

Mrna Transcript ◽

Aldosterone Secretion ◽

Glomerulosa Cells ◽

Whole Cell Recordings ◽

Expression Signal ◽

Zona Glomerulosa Cells

The low voltage-activated (T-type) Ca2+ channel has been implicated in the regulation of aldosterone secretion from the adrenal zona glomerulosa by extracellular K+ levels, angiotensin II, and ACTH. However, the identity of the specific subtype mediating this regulation has not been determined. We utilized in situ hybridization to examine the distribution of three newly cloned members of the T-type Ca2+ channel family, α1G, α1H, and α1I, in the rat and bovine adrenal gland. Substantial expression of only the mRNA transcript for the α1H-subunit was detected in the zona glomerulosa of both rat and bovine. A much weaker expression signal was detected for the α1H transcript in the zona fasciculata of bovine. Whole cell recordings of isolated bovine adrenal zona glomerulosa cells showed the native low voltage-activated current to be inhibited by NiCl2 with an IC50 of 6.4 ± 0.2 μM. Because the α1H subtype exhibits similar NiCl2 sensitivity, we propose that the α1Hsubtype is the predominant T-type Ca2+ channel present in the adrenal zona glomerulosa.

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Inhibition of aldosterone release by hypoxia in vitro: interaction with carbon monoxide

Journal of Applied Physiology ◽

10.1152/jappl.1994.76.2.689 ◽

1994 ◽

Vol 76 (2) ◽

pp. 689-693 ◽

Cited By ~ 3

Author(s):

H. Raff ◽

B. Jankowski

Keyword(s):

Carbon Monoxide ◽

Angiotensin Ii ◽

Zona Glomerulosa ◽

Michaelis Constant ◽

Aldosterone Synthase ◽

Aldosterone Production ◽

Glomerulosa Cells ◽

In Vitro Interaction ◽

Zona Glomerulosa Cells

We have demonstrated that the aldosteronogenic pathway of the zona glomerulosa is unusually sensitive to modest changes in PO2 (Michaelis constant for O2 approximately 95 Torr). The current study evaluated the interaction of CO (the classic ligand for P-450 enzymes) and the decreases in O2 on aldosteronogenesis in vitro. Bovine adrenocortical zona glomerulosa cells were incubated for 2 h and stimulated with either adenosine 3′,5′-cyclic monophosphate (cAMP) or angiotensin II. Ten and 20% CO led to significant decreases in cAMP- and angiotensin II-stimulated aldosteronogenesis. The combination of 20% CO and moderate decreases in PO2 (from approximately 140 to approximately 100 Torr) led to an interactive decrease in aldosterone production. The conversion of corticosterone to aldosterone catalyzed by aldosterone synthase, which is the site of O2 sensitivity, was not significantly inhibited by CO. We conclude that the aldosterone pathway is not exceptionally sensitive to CO compared with other steroidogenic pathways. This observation suggests that the unique O2-sensitive properties of the aldosterone pathway located primarily within aldosterone synthase may not reside in its CO binding site (i.e., heme).

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