Cholecystokinin (CCK) stimulates aldosterone secretion from human adrenocortical cells via CCK2 receptors coupled to the adenylate cyclase/protein kinase A signaling cascade.
Cholecystokinin (CCK) IS a regulatory peptide that acts via two receptor subtypes, CCK1-R and CCK2-R. RT-PCR demonstrated the expression of both CCK1-R and CCK2-R in the zona glomerulosa (ZG), but not zona fasciculata-reticularis cells of the human adrenal cortex. CCK and the CCK2-R agonist pentagastrin enhanced basal aldosterone secretion from ZG cells without affecting cortisol production from zona fasciculata-reticularis cells. The aldosterone response to CCK and pentagastrin was suppressed by a CCK2-R antagonist, but not by a CCK1-R antagonist. Pentagastrin evoked a sizeable cAMP, but not inositol triphosphate, response from ZG cells, whereas CCK plus CCK2-R antagonist was ineffective. The cAMP response to pentagastrin was abrogated by CCK2-R antagonist or the adenylate cyclase inhibitor SQ-22536, and the aldosterone response was abolished by both SQ-22536 and the protein kinase A inhibitor H-89. Both CCK and pentagastrin increased steroidogenic acute regulatory protein mRNA expression in ZG cells; the effect was abrogated by CCK2-R antagonist. We conclude that CCK exerts secretagogue action on human ZG cells, acting through CCK2-Rs coupled to the adenylate cyclase/protein kinase A signaling cascade, which, in turn, stimulates the expression of steroidogenic acute regulatory protein, the rate-limiting step of steroidogenesis.
Mazzocchi
G
G
Department of Human Anatomy and Physiology, Section of Anatomy, University of Padua, I-35121 Padua, Italy.
Malendowicz
L K
LK
Aragona
F
F
Spinazzi
R
R
Nussdorfer
G G
GG
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000302:Adrenal Cortex / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D000328:Adult; D000450:Aldosterone / Q000378:metabolism*; D002766:Cholecystokinin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D008875:Middle Aged; D010418:Pentagastrin / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D043886:Receptor, Cholecystokinin A / Q000235:genetics / Q000378:metabolism; D043887:Receptor, Cholecystokinin B / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D007295:Inositol Phosphates; D012333:RNA, Messenger; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D000450:Aldosterone; D002766:Cholecystokinin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases; D010418:Pentagastrin