Effect of atrial natriuretic peptide on ACTH, dibutyryl cAMP, angiotensin II and potassium-stimulated aldosterone secretion by rat adrenal glomerulosa cells.
We examined the effect of rat atrial natriuretic peptide (ANP) on ACTH, dibutyryl cAMP, angiotensin II and potassium-stimulated aldosterone secretion by dispersed rat adrenal glomerulosa cells. ANP inhibited ACTH, angiotensin II and potassium-stimulated aldosterone secretion with IC50's between 0.15-0.20 nM. Inhibition by 10 nM ANP could not be overcome with higher concentrations of these stimuli. ANP shifted the dibutyryl cAMP dose-response curve slightly to the right but did not blunt the maximal aldosterone secretory response. The sites of ANP inhibition in the aldosterone biosynthetic pathway for these stimuli were also examined. ANP inhibited activation of the cholesterol desmolase (CD) enzyme complex by ACTH, angiotensin II and potassium. Activation of the corticosterone methyl oxidase (CMO) enzyme complex by potassium was inhibited by ANP, however, activation by ACTH was not blocked. We concluded that: 1) ANP is a potent inhibitor of ACTH, angiotensin II and potassium-stimulated aldosterone secretion; 2) inhibition of ACTH stimulation is primarily due to lower cAMP levels and; 3) inhibition of angiotensin II and potassium stimulation reflects a block in the activating mechanism of the CMO and/or CD enzyme complexes, whereas CD but not CMO activation by ACTH is inhibited by ANP.
Schiebinger
R J
RJ
Oklahoma University Health Sciences Center, Oklahoma City.
Kem
D C
DC
Brown
R D
RD
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000450:Aldosterone / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D003994:Bucladesine / Q000494:pharmacology*; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000037:antagonists & inhibitors / Q000378:metabolism; D019405:Cytochrome P-450 CYP11B2; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology*; D011284:Pregnenolone / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000804:Angiotensin II; D000450:Aldosterone; D003994:Bucladesine; D011284:Pregnenolone; D009320:Atrial Natriuretic Factor; D000324:Adrenocorticotropic Hormone; D006899:Mixed Function Oxygenases; D019405:Cytochrome P-450 CYP11B2; C033112:corticosterone methyl oxidase I; C025352:corticosterone methyl oxidase II; D002786:Cholesterol Side-Chain Cleavage Enzyme; D011188:Potassium