title: Cholera-toxin and corticotropin modulation of inositol phosphate accumulation induced by vasopressin and angiotensin II in rat glomerulosa cells.
abstract: Vasopressin (VP) and angiotensin II (AT II) stimulate the production of inositol phosphates (IP) in rat glomerulosa cells. Guanosine 5'-[gamma-thio]triphosphate (GTP[S]), but not VP or AT II, stimulates IP production in a myo-[3H]inositol-prelabelled glomerulosa-cell membrane preparation. In combination with GTP[S], these hormones potentiate the response to GTP[S], indicating the existence of a G-protein involved in the coupling of the VP and AT II receptor with the phospholipase C. ADP-ribosylation with pertussis toxin (IAP) revealed the specific labelling of a single molecule of 41 kDa. No significant inhibition of VP- or AT II-stimulated IP accumulation was detected in intact cells when the whole 41 kDa molecule was endogenously ADP-ribosylated by IAP treatment. On the contrary, when glomerulosa cells were infected with cholera toxin (CT), both the VP- and AT II-stimulated IP accumulations were inhibited in a dose-dependent manner. Yet these effects were partial even at high concentrations of CT, and could not be related to the ADP-ribosylation of 'alpha s' molecules. Similarly, when the cells were infected with 1 microgram of CT/ml, the specific binding of VP and AT II decreased by 50-60%. Such results may signify that the treatment primarily affects the densities of the hormone receptors. When glomerulosa cells were incubated for 15 h in the presence of 10 nM-corticotropin (ACTH), a condition in which the intracellular concentration of cyclic AMP was increased 3-fold, the maximum IP response to 0.1 microM-VP or -AT II was decreased by 50%. When similar experiments were carried out only after a 15 min incubation period with the same concentration of ACTH, the increase in cyclic AMP was more pronounced, but no inhibition of hormone-induced IP accumulation was observed. Altogether, these results may suggest that CT exerts its action on the VP- or AT II-sensitive phospholipase C systems via a prolonged increase in intracellular cyclic AMP.
authors.affiliation: Centre CNRS-INSERM de Pharmacologie-Endocrinologie, Montpellier, France.
authors.forename: G
authors.initials: G
authors.lastname: Guillon
authors.forename: N
authors.initials: N
authors.lastname: Gallo-Payet
authors.forename: M N
authors.initials: MN
authors.lastname: Balestre
authors.forename: C
authors.initials: C
authors.lastname: Lombard
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D007294:Inositol / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism*; D051381:Rats; D013403:Sugar Phosphates / Q000378:metabolism*; D010738:Type C Phospholipases / Q000096:biosynthesis
chemical_list: D007295:Inositol Phosphates; D013403:Sugar Phosphates; D000804:Angiotensin II; D001127:Arginine Vasopressin; D007294:Inositol; D000244:Adenosine Diphosphate; D000324:Adrenocorticotropic Hormone; D002772:Cholera Toxin; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins