Angiotensin II stimulates growth and steroidogenesis in zona fasciculata/reticularis cells from bovine adrenal cortex via the AT1 receptor subtype.
Primary cultures of bovine adrenocortical zona fasciculata/reticularis (zfr) cells responded to angiotensin II (AII) with a dose-dependent increase in [3H]thymidine incorporation into DNA. The effect was maximal at 100 nmol/liter AII, and was dose dependently inhibited by (sar1, ala8)-AII (saralasin) and DuP753, but not by PD123177. Both AII-stimulated cortisol secretion and phosphoinositidase C activity were also inhibited by saralasin and DuP753, but not by PD123177. Pharmacological analysis of the antagonism of AII-stimulated cortisol secretion by saralasin and DuP753 produced pA2 values of 8.79 and 7.02, respectively. Whereas the pA2 for saralasin agreed closely with previous measurements in other systems, DuP753 was at least one order of magnitude less potent in inhibiting the action of AII in bovine zfr cells compared to previous measurements in rabbit vascular smooth muscle. We conclude that the steroidogenic and mitogenic effects of AII in bovine zfr cells are mediated by the AT1 receptor.
Edinburgh University, Department of Pharmacology, United Kingdom.
C D
CD
Clyne
M R
MR
Nicol
S
S
MacDonald
B C
BC
Williams
S W
SW
Walker
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006854:Hydrocortisone / Q000096:biosynthesis*; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D012504:Saralasin / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology; D015383:Zona Fasciculata / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015385:Zona Reticularis / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D010727:Phosphoric Diester Hydrolases; C021491:glycerophosphoinositol glycerophosphodiesterase; D012504:Saralasin; D019808:Losartan; D006854:Hydrocortisone