Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 3 de 3
Filter
Add more filters










Database
Publication year range
2.
Life Sci ; 63(26): 2313-21, 1998.
Article in English | MEDLINE | ID: mdl-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.


Subject(s)
Adrenal Cortex/drug effects , Aldosterone/metabolism , Angiotensin II/pharmacology , Antihypertensive Agents/pharmacology , Membrane Proteins/physiology , Peptide Fragments/pharmacology , Peptides/pharmacology , Receptors, Peptide , Adrenal Cortex/metabolism , Adrenomedullin , Adult , Dose-Response Relationship, Drug , Humans , Middle Aged , Receptors, Adrenomedullin , Structure-Activity Relationship
SELECTION OF CITATIONS
SEARCH DETAIL
...