Adrenomedullin and calcitonin gene-related peptide inhibit aldosterone secretion in rats, acting via a common receptor.
Adrenomedullin (ADM) and calcitonin gene-related peptide (CGRP) did not affect either basal or ACTH-stimulated secretion of a1dosterone and corticosterone by dispersed rat capsular and inner adrenocortical cells, respectively. However, both peptides strongly depressed angiotensin-II (ANG- II)-stimulated a1dosterone production by capsular cells, the minimal effective concentration was 10(-7) M. The inhibitory effect of both ADM and CGRP was reversed by CGRP8-37, a specific CGRP1 receptor antagonist; a complete reversal was obtained with a CGRP8-37 concentration of 10(-6) M. Our findings indicate that ADM and CGRP specifically interfere with the intracellular mechanisms transducing the secretagogue signal of ANG-II, and suggest that the ADM effect is mediated by CGRP receptors
Mazzocchi
G
G
Department of Anatomy, University of Padua, Italy.
Rebuffat
P
P
Gottardo
G
G
Nussdorfer
G G
GG
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D053607:Adrenomedullin; D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D002478:Cells, Cultured; D003345:Corticosterone / Q000378:metabolism; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000187:drug effects / Q000502:physiology*; D015383:Zona Fasciculata / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D015384:Zona Glomerulosa / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure
D000959:Antihypertensive Agents; D010455:Peptides; D018015:Receptors, Calcitonin Gene-Related Peptide; D053607:Adrenomedullin; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D015740:Calcitonin Gene-Related Peptide; D003345:Corticosterone