title: Angiotensin II and guanine nucleotides stimulate formation of inositol 1,4,5-trisphosphate and its metabolites in permeabilized adrenal glomerulosa cells.
abstract: Angiotensin II (AII) interacts with specific receptors in the adrenal glomerulosa cell and stimulates the hydrolysis of plasma membrane phosphoinositides by phospholipase C, with production of inositol 1,4,5-trisphosphate (Ins-1,4,5-P3) and subsequent mobilization of intracellular Ca2+. In electrically permeabilized, [3H]inositol-labeled glomerulosa cells, AII stimulated Ins-1,4,5-P3 production within 15 s with half-maximal potency of 10(-9) M. The nonhydrolyzable GTP analog, guanosine 5'-O-thiotriphosphate (GTP gamma S), stimulated Ins-1,4,5-P3 formation in a dose-dependent manner with half-maximal effect at 10(-7) M. AII-activated Ins-1,4,5-P3 production was further increased by guanine nucleotides. The rate at which GTP gamma S-stimulated inositol polyphosphate production was consistently slower than that of AII. In adrenal membrane preparations, GTP gamma S-stimulated polyphosphoinositide hydrolysis was enhanced by Ca2+, with half-maximal activity at 300 nM free Ca2+. Ins-1,4,5-P3 formation was also increased by NaF, further indicating the involvement of a guanine nucleotide regulatory protein. In addition to Ins-1,4,5-P3 and its metabolites formed during degradation via the 4-monophosphate pathway, AII and GTP gamma S stimulated the formation of the phosphorylated metabolite inositol 1,3,4,5-tetrakisphosphate and inositol 1,3,4-trisphosphate in permeabilized cells. The absence of a significant rise in inositol 1-monophosphate indicated that phosphatidylinositol hydrolysis was not stimulated by AII or GTP gamma S. Pretreatment of glomerulosa cells with pertussis toxin for 12 h before permeabilization did not inhibit AII- or GTP gamma S-stimulated inositol polyphosphate formation. However, treatment with cholera toxin, forskolin, or 8-Br-cAMP for 12 h enhanced both basal and ligand-stimulated Ins-1,4,5-P3 production. These observations suggest that agonist binding to the AII receptor activates a polyphosphoinositide-specific phospholipase C in the adrenal glomerulosa cell, and that a distinctive guanine regulatory protein is involved in this mechanism.
authors.affiliation: Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892.
authors.forename: A J
authors.initials: AJ
authors.lastname: Baukal
authors.forename: T
authors.initials: T
authors.lastname: Balla
authors.forename: L
authors.initials: L
authors.lastname: Hunyady
authors.forename: W
authors.initials: W
authors.lastname: Hausdorff
authors.forename: G
authors.initials: G
authors.lastname: Guillemette
authors.forename: K J
authors.initials: KJ
authors.lastname: Catt
mesh_terms: D000302:Adrenal Cortex / Q000187:drug effects* / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002417:Cattle; D002463:Cell Membrane Permeability; D002772:Cholera Toxin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006150:Guanine Nucleotides / Q000494:pharmacology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000378:metabolism*; D037342:Pertussis Toxin; D012969:Sodium Fluoride / Q000494:pharmacology; D013403:Sugar Phosphates / Q000378:metabolism*; D013873:Thionucleotides / Q000494:pharmacology; D013997:Time Factors; D010738:Type C Phospholipases / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D006150:Guanine Nucleotides; D007295:Inositol Phosphates; D013403:Sugar Phosphates; D013873:Thionucleotides; D010566:Virulence Factors, Bordetella; D000804:Angiotensin II; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D015544:Inositol 1,4,5-Trisphosphate; D006160:Guanosine Triphosphate; D012969:Sodium Fluoride; D002772:Cholera Toxin; D037342:Pertussis Toxin; D010738:Type C Phospholipases; D002118:Calcium