Lack of effect of angiotensin on levels of cyclic AMP in isolated adrenal zona glomerulosa cells from the rat.

The effects of pure [Asp1,Val5]- and [Asn1,Val5]-angiotensin II and also [des-Asp1,Ile5]-angiotensin II (angiotensin III) on cyclic AMP and steroid outputs by dispersed rat capsular cells, comprising 95% zona glomerulosa and 5% zona fasciculata cells, have been studied. The results showed that [Asp1, Val5]-and [Asn1, VAl5]-angiotensin II, at doses between 2.5 X 10(-11) and 2 X 10(-4) mol/l, which produced typical increases in steroidogenesis, failed to increase output of cyclic AMP. This lack of effect was observed whether the nucleotide was measured by radioimmunoassay or by adrenal binding protein and under the same conditions in which 8.4 mM-K+ consistently increased the output of cyclic AMP. Instead the results showed a small but significant decrease in cyclic AMP output with angiotensin II. Similar results were obtained with incubations for 60 rather than 120 min and with medium containing a concentration of 5 or 40 g bovine serum albumin/l. Although the levels of cyclic AMP were generally higher in the presence of the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, the same decrease relative to basal outputs was observed with angiotensin II which increased steroidogenesis. Angiotensin III also failed to increase output of cyclic AMP at doses (2.5 X 10(-9) to 2.5 X 10(-6) mol/l) which produced increases in steroid output equivalent to those with angiotensin II. These results indicate that angiotensin II and III can act through a cyclic AMP-independent mechanism.