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Inhibitory Effect of Adrenomedullin (ADM) on the Aldosterone Response of Human Adrenocortical Cells to angiotensin-II: Role of ADM(22-52)-sensitive Receptors

Inhibitory Effect of Adrenomedullin (ADM) on the Aldosterone Response of Human Adrenocortical Cells to angiotensin-II: Role of ADM(22-52)-sensitive Receptors

A S Belloni, P G Andreis, G P Rossi, A Mingrino, H C Champion, P J Kadowitz, W A Murphy, D H Coy, G G Nussdorfer

Life Sci. 1998;63(26):2313-21.

PMID: 9877221

Abstract:

Human adrenomedullin (ADM) is a 52-amino acid hypotensive peptide, which possesses a disulfide bridge-formed six-membered ring in 16-21 position. The ring structure, and both the N- and C-terminal amino-acid sequences seem to play a key role in the vascular effects of ADM(1-52), and we have investigated whether the same is true for the inhibitory effect of this peptide on the aldosterone response of zona glomerulosa (ZG) cells to angiotensin-II (ANG-II). Autoradiography showed the presence of abundant [125I]ADM(1-52) binding sites in the ZG of human adrenals, which were displaced not only by cold ADM(1-52), but also by both ADM(13-52) and ADM(22-52); ADM fragments 1-12, 15-22 and 16-31 were ineffective. ADM(1-52) and ADM(13-52), but not other fragments, concentration-dependently inhibited ANG-II-stimulated aldosterone secretion of dispersed human adrenocortical cells. The aldosterone antisecretagogue actions of ADM(1-52) and ADM(13-52) were counteracted by ADM(22-52) in a concentration-dependent manner, while other ADM fragments were ineffective. In light of these findings the following conclusions could be drawn: (i) human ZG cells are provided with ADM(22-52)-sensitive receptors; (ii) the six-membered ring structure and the C-terminal, but not N-terminal, amino-acid sequence are both essential for ADM(1-52) to exert its antimineralocorticoid action; and probably (iii) the C-terminal sequence is needed for ADM(1-52) to bind its ZG receptors, while the ring structure is required for the receptor activation.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP159899657	Adrenomedullin Fragment 22-52 human		159899-65-7	Price

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