Corticotropin-inhibiting peptide enhances aldosterone secretion by dispersed rat zona glomerulosa cells.
Corticotropin-inhibiting peptide (CIP), the 7-38 fragment of human ACTH(1-39), is known to act as an antagonist of ACTH receptors. Accordingly, CIP has been found to inhibit ACTH-stimulated glucocorticoid secretion of dispersed rat adrenocortical cells, without per se affecting the basal production. We confirmed these findings, but unexpectedly observed that CIP concentration-dependently raised basal aldosterone secretion from fresh suspensions of rat zona glomerulosa (ZG) cells, maximal effective concentration being 10(-6) M. CIP (10(-6) M) partially reversed the ZG-cell response to ACTH, but not to the Ca2+-dependent agonists angiotensin-II (ANG-II) and K+. The aspecific ANG-II-receptor antagonist saralasin (10(-6) M) blocked the aldosterone response of ZG cells to 10(-6) M CIP, and in the presence of the Ca2+-channel blocker verapamil CIP was ineffective. Collectively, these findings suggest that CIP enhances aldosterone secretion of rat ZG through a mechanism involving the activation of ANG-II receptors and the consequent rise in the cytosolic Ca2+ concentration. They also stress that this side-effect of CIP must be taken into account in interpreting the results of investigations on the adrenal cortex, where CIP has been employed as an ACTH-receptor antagonist.
Malendowicz
L K
LK
Department of Histology and Embryology, School of Medicine, Poznan, Poland.
Rebuffat
P
P
Nussdorfer
G G
GG
Nowak
K W
KW
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000450:Aldosterone / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology*; D006801:Humans; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012504:Saralasin / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology; D015384:Zona Glomerulosa / Q000378:metabolism*
D006727:Hormone Antagonists; D010446:Peptide Fragments; D000804:Angiotensin II; D000450:Aldosterone; C026034:ACTH (7-38); D000324:Adrenocorticotropic Hormone; D014700:Verapamil; D012504:Saralasin