Ovine adrenal fasciculata cells contain angiotensin-II receptors coupled to intracellular effectors but are resistant to the steroidogenic effects of this hormone.
Ovine adrenal fasciculata cells (OAC) responded to ACTH but were resistant to the steroidogenic action of angiotensin-II (A-II), while bovine adrenal fasciculata cells (BAC) responded to this hormone as well as to ACTH. However both cell types contained specific A-II binding sites (120,000 +/- 14,000 and 85,000 +/- 10,000 sites per cell for OAC and BAC, respectively) of similar high affinity [dissociation constant (KD) congruent to 2 x 10(-9) M]. Moreover, in both cell types, A-II receptors were coupled to intracellular effectors since A-II: 1) stimulated the accumulation of inositol phosphates, although the effects in BAC were higher than in OAC; 2) enhanced the influx and the efflux of 45Ca2+; 3) increased cytosolic free Ca2+ concentration ([Ca2+]i); 4) potentiated ACTH-induced cAMP production; and 5) induced A-II receptor loss. Both cell types appear to have an active protein kinase C since the phorbol ester 4 beta-phorbol 12-myristate-13-acetate potentiates ACTH-induced cAMP production and caused A-II receptor loss. In addition, 4 beta-phorbol 12-myristate-13-acetate and Ca2+ ionophore enhanced the steroid production by BAC but had no effect on OAC. These results indicated that the steroidogenic refractoriness of OAC to A-II might involve some step(s) beyond the initial activation of the two branches of the phosphoinositide pathway, activation of protein kinase C and increase of [Ca2+]i, and before conversion of cholesterol to pregnenolone.
Viard
I
I
INSERM U 307, Hôpital Debrousse, Lyon, France.
Rainey
W E
WE
Capponi
A M
AM
Begeot
M
M
Saez
J M
JM
D000311:Adrenal Glands / Q000166:cytology / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D004789:Enzyme Activation; D007295:Inositol Phosphates / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D009994:Osmolar Concentration; D011493:Protein Kinase C / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000378:metabolism*; D012756:Sheep; D013256:Steroids / Q000096:biosynthesis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007295:Inositol Phosphates; D011945:Receptors, Angiotensin; D013256:Steroids; D000804:Angiotensin II; D000324:Adrenocorticotropic Hormone; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium