Volume 5 Supplement 1

2nd International Conference of cGMP Generators, Effectors and Therapeutic Implications

Open Access

Inhibition of agonist-stimulated aldosterone production from adrenal zona glomerulosa cells by ANP is mediated by GC-A

BMC Pharmacology20055(Suppl 1):P19

DOI: 10.1186/1471-2210-5-S1-P19

Published: 16 June 2005

Atrial natriuretic peptide (ANP) is a potent inhibitor of agonist-induced aldosterone synthesis in zona glomerulosa (ZG) cells of the adrenal gland. Cellular ANP effects are mediated by two receptors: GC-A, a membrane guanylyl cyclase, and GC-C that lacks guanylyl cyclase activity. To identify which one of these two receptors is involved in inhibitory pathway of aldosterone production we developed a new model of isolation and primary culture of mouse ZG cells. Aldosterone concentration in the blood was not different in wild type and GC-A knockout mice. ANP (10 nM) significantly inhibited basal, forskolin, and Angiotensin II-stimulated aldosterone production from wild type mice, while in GC-A knockout mice ANP had no inhibitory effect on aldosterone production. Inhibition of forskolin or ACTH stimulated aldosterone production by ANP was connected with increased concentration of cGMP, stimulation of cGMP-stimulated phosphodiesterase (PDE2), and decrease of intracellular cAMP content. IBMX and the PDE2-selective inhibitor MEP-1 completely prevented ANP inhibitory effect on cAMP-stimulated aldosterone production. In contrast, ANP-dependent inhibition of Ang II-stimulated aldosterone production was not connected with PDE2 or PKG activity indicating that other cGMP-dependent mediator(s)/mechanism(s) are involved in regulation of Ang II-stimulated aldosterone production from ZG cells by cGMP.

Declarations

Acknowledgements

This work was supported by the Deutsche Forschungsgemeinschaft grant WA 366

Authors’ Affiliations

(1)
Institute of Clinical Biochemistry and Pathobiochemistry, University of Wuerzburg
(2)
Institute of Physiology University of Wuerzburg

Copyright

© BioMed Central Ltd 2005

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