Angiotensin-II activation of cAMP and corticosterone production in bovine adrenocortical cells: effects of nonpeptide angiotensin-II antagonists.
The ability of angiotensin-II (A-II) to increase cAMP production in adrenocortical cells is not widely accepted due to numerous conflicting reports. The recent observation that rat adrenal cells exhibit multiple subtypes of A-II receptors raises the possibility that a specific subtype could be responsible for controlling cAMP stimulation. In the present study we characterize in detail the effects of A-II on cAMP production in bovine adrenocortical zona fasciculata cells (BAC) cells and determined which A-II receptor subtype is responsible for stimulating both cAMP production and steroidogenesis. A-II (100 nM) increased the medium content of cAMP by 5- to 10-fold. The magnitude of A-II stimulation, while significant, was considerably less than that observed following treatment with ACTH (100 nM) (10-fold vs. 500-fold). The A-II stimulation of cAMP was both concentration and time dependent with a significant increase in cAMP observed in the presence of 1 nM A-II and a maximal response observed using 100 nM A-II. Stimulation was also seen using the decapeptide, A-I, and the heptapeptide, A-III. Of the angiotensin analogues tested, the order of potency was A-II greater than A-III greater than A-I. The A-II antagonist, [Sar1, Ala8]-A-II (saralasin), reversed the stimulatory effect of A-II. The superior potency of A-II and the ability of saralasin to inhibit cAMP production suggest a specific receptor mediated mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)
Rainey
W E
WE
Department of Obstetrics and Gynecology and Biochemistry, University of Texas, Southwestern Medical Center, Dallas 75235-9032.
Byrd
E W
EW
Sinnokrot
R A
RA
Carr
B R
BR
D000302:Adrenal Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000805:Angiotensin III / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D002417:Cattle; D003345:Corticosterone / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D011725:Pyridines / Q000494:pharmacology; D012504:Saralasin / Q000494:pharmacology*; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D011725:Pyridines; D013777:Tetrazoles; D000804:Angiotensin II; D000805:Angiotensin III; C073402:PD 123319; D000803:Angiotensin I; D000242:Cyclic AMP; D012504:Saralasin; D019808:Losartan; D003345:Corticosterone