title: Control of aldosterone production by angiotensin II is mediated by two guanine nucleotide regulatory proteins.
abstract: The involvement of guanine nucleotide regulatory proteins in the steroidogenic response of the adrenal glomerulosa to angiotensin II (AII) was investigated by analyzing the effects of Bordetella pertussis toxin (PT) on several aspects of AII action. These included receptor binding, stimulation of aldosterone production and GTPase activity, inhibition of cAMP production, and attenuation of the aldosterone response at high angiotensin concentrations. Pretreatment of glomerulosa cells with PT abolished the inhibitory effects of both AII and somatostatin (SRIF) on ACTH-stimulated cAMP production. Under the same incubation conditions, the stimulation of aldosterone secretion by submaximal and maximal steroidogenic concentrations of AII was completely unaffected by the toxin. However, the attenuation of steroid responses seen with supramaximal concentrations of AII was abolished. In addition, the ability of SRIF to inhibit AII-stimulated steroid production was markedly reduced by PT treatment. The binding of [125I]AII to high affinity sites in intact cells and particulate fractions, and modulation of the binding by guanine nucleotides, were unaffected by toxin pretreatment, even under conditions where a 40-41K protein was completely ADP ribosylated. In contrast, the toxin substantially diminished the binding of [125I]Tyr0-SRIF to SRIF receptors in glomerulosa cells (by 50% after 5 h and by 90% after 20 h). These results indicate that Ni or a similar protein probably mediates the inhibition of cAMP formation by AII and the attenuation of the steroid response by high concentrations of AII as well as the inhibitory actions of SRIF in the adrenal glomerulosa cell. Furthermore, the lack of effect of PT on AII binding and stimulation of GTPase activity suggests the existence of an additional pertussis-insensitive guanine nucleotide-regulatory protein that is activated by lower concentrations of AII and mediates the stimulation of aldosterone production.
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000450:Aldosterone / Q000096:biosynthesis*; D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000242:Cyclic AMP / Q000096:biosynthesis; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000502:physiology*; D006150:Guanine Nucleotides / Q000494:pharmacology; D008297:Male; D037342:Pertussis Toxin; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D017481:Receptors, Somatostatin; D013004:Somatostatin / Q000378:metabolism / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D006150:Guanine Nucleotides; D011945:Receptors, Angiotensin; D017981:Receptors, Neurotransmitter; D017481:Receptors, Somatostatin; D010566:Virulence Factors, Bordetella; D000804:Angiotensin II; D000246:Adenosine Diphosphate Ribose; D000450:Aldosterone; D013004:Somatostatin; D000242:Cyclic AMP; D037342:Pertussis Toxin; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins