Angiotensin II(A-II) steroidogenic refractoriness in Y-1 cells in the presence of A-II receptors negatively coupled to adenylate cyclase

Abstract

Y₁ adrenal tumor cells are resistant to the steroidogenic effect of A-II though they possess specific A-II binding sites. The number of these binding sites is lower in Y₁ cells than in bovine adrenal cells, but the affinity is similar in the two models. Moreover, Y₁ cells are shown to contain a high level of cytosolic protein kinase C whose properties appear similar to those observed in bovine adrenal cells. However, the activation of protein kinase C by a phorbol ester (PMA) or diacylglycerol (OAG) does not induce steroidogenesis in Y₁ cells. On the other hand, A-II, without any effect on adenylate cyclase in basal conditions, reduces the ACTH-induced cAMP production in Y₁ cells. This inhibitory effect of A-II is not blocked by phosphodiesterase inhibitor but is completely abolished after 24 hours of pretreatment of intact cells with pertussis toxin. This inhibition is probably mediated by the inhibitory guanine nucleotide regulatory protein (Gi) since the labeled 41 KD-ADP ribosylated protein disappeared after 24 hours of pretreatment of intact cells with pertussis toxin. Moreover, the accumulation of inositol phosphates under A-II stimulation was low, which suggests that the coupling of A-II receptors with phospholipase C is reduced in Y₁ cells. The Y₁ cell line is probably a good model to study the post membrane events in A-II action.

Key Words:

• Y.₁ adrenal tumor cell line
• angiotensin-II receptors
• steroidogenesis
• protein kinase C.