title: Angiotensin II receptors and mechanisms of action in adrenal glomerulosa cells.
abstract: The plasma-membrane receptors, coupling mechanisms, and effector enzymes that mediate target-cell activation by angiotensin II (AII) have been characterized in rat and bovine adrenal glomerulosa cells. The AII holoreceptor is a glycoprotein of Mr approximately 125,000 under non-denaturing conditions. Photoaffinity labeling of AII receptors with azido-AII derivatives has shown size heterogeneity among the AII binding sites between species and target tissues, with Mr values of 55,000 to 79,000. Such variations in molecular size probably reflect differences in carbohydrate content of the individual receptor sites. The adrenal AII receptor, like that in other tissues, is coupled to the inhibitory guanine nucleotide inhibitory protein (Ni). However, studies with pertussis toxin have shown that stimulation of aldosterone production by AII is not mediated by Ni but by a pertussis-insensitive nucleotide regulatory protein of unidentified nature. Although Ni is not involved in the stimulatory action of AII on steroidogenesis, it does mediate the inhibitory effects of high concentrations of AII upon aldosterone production. The actions of AII on adrenal cortical function are thus regulated by at least two guanine nucleotide regulatory proteins that are selectively activated by increasing AII concentrations. The principal effector enzyme in AII action is phospholipase C, which is rapidly stimulated in rat and bovine glomerulosa after AII receptor activation. AII-induced breakdown of phosphatidylinositol bisphosphate (PIP2) and phosphatidylinositol phosphate (PIP) leads to formation of inositol 1,4,5-trisphosphate (IP3) and inositol 1,4-bisphosphate (IP2). These are metabolized predominantly to inositol-4-monophosphate, which serves as a marker of polyphosphoinositide breakdown, whereas inositol-1-phosphate is largely derived from phosphatidylinositol hydrolysis. The AII-stimulated glomerulosa cell also produces inositol 1,3,4-trisphosphate, a biologically inactive IP3 isomer formed from Ins-1,4,5-trisphosphate via inositol tetrakisphosphate (IP4) during ligand activation in several calcium-dependent target cells. The Ins-1,4,5-P3 formed during AII action binds with high affinity to specific intracellular receptors that have been characterized in the bovine adrenal gland and other AII target tissues, and may represent the sites through which IP3 causes calcium mobilization during the initiation of cellular responses.
authors.affiliation: Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, Bethesda, MD 20892.
authors.forename: K J
authors.initials: KJ
authors.lastname: Catt
authors.forename: M C
authors.initials: MC
authors.lastname: Carson
authors.forename: W P
authors.initials: WP
authors.lastname: Hausdorff
authors.forename: C M
authors.initials: CM
authors.lastname: Leach-Harper
authors.forename: A J
authors.initials: AJ
authors.lastname: Baukal
authors.forename: G
authors.initials: G
authors.lastname: Guillemette
authors.forename: T
authors.initials: T
authors.lastname: Balla
authors.forename: G
authors.initials: G
authors.lastname: Aguilera
mesh_terms: D000311:Adrenal Glands / Q000187:drug effects / Q000502:physiology*; D000450:Aldosterone / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D015220:Calcium Channels; D019204:GTP-Binding Proteins / Q000502:physiology; D053496:Inositol 1,4,5-Trisphosphate Receptors; D010716:Phosphatidylinositols / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D010716:Phosphatidylinositols; D011945:Receptors, Angiotensin; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D000804:Angiotensin II; D000450:Aldosterone; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins