Cholecystokinin stimulates aldosterone secretion from dispersed rat zona glomerulosa cells, acting through cholecystokinin receptors 1 and 2 coupled with the adenylate cyclase-dependent cascade.
Cholecystokinin is a regulatory peptide, that acts through two subtypes of receptors, 1 and 2. RT-PCR demonstrated the expression of both cholecystokinin receptors 1 and 2 genes in the zona glomerulosa, but not the zona fasciculata-reticularis, of rat adrenals. Autoradiography demonstrated the presence of abundant [(125)I]cholecystokinin-binding sites in the zona glomerulosa, but not the zona fasciculata-reticularis, which were displaced by both cholecystokinin receptor 1- and 2-selective antagonists (cholecystokinin 1-A and 2-A). Cholecystokinin increased basal aldosterone secretion from dispersed zona glomerulosa cells without affecting corticosterone secretion from zona fasciculata-reticularis cells. The aldosterone response to cholecystokinin was blunted by cholecystokinin 1-A and 2-A, which when added together abolished it. ACTH-stimulated aldosterone production was not affected by cholecystokinin; in contrast, cholecystokinin potentiated aldosterone response to both angiotensin II and K(+). Cholecystokinin enhanced cAMP, but not IP(3), release by dispersed zona glomerulosa cells. The aldosterone response to cholecystokinin was abolished by the adenylate cyclase inhibitor SQ-22536 and the PKA inhibitor H-89, but not by either the PLC inhibitor U-73122 or the PKC inhibitor calphostin C. In conclusion, our study provides evidence that cholecystokinin, acting through cholecystokinin receptors 1 and 2 coupled with the adenylate cyclase/PKA cascade, exerts a sizeable secretagogue action on rat zona glomerulosa cells.
Malendowicz
L K
LK
Department of Histology and Embryology, School of Medicine, PL-60781 Poznan, Poland.
Nowak
M
M
Gottardo
L
L
Tortorella
C
C
Majchrzak
M
M
Nussdorfer
G G
GG
D000262:Adenylyl Cyclases / Q000502:physiology; D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D002766:Cholecystokinin / Q000494:pharmacology*; D005260:Female; D051381:Rats; D017208:Rats, Wistar; D011949:Receptors, Cholecystokinin / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D015384:Zona Glomerulosa / Q000502:physiology*
D011949:Receptors, Cholecystokinin; D000450:Aldosterone; D002766:Cholecystokinin; D000262:Adenylyl Cyclases