title: Bradykinin-activated transmembrane signals are coupled via No or Ni to production of inositol 1,4,5-trisphosphate, a second messenger in NG108-15 neuroblastoma-glioma hybrid cells.
abstract: The addition of bradykinin to NG108-15 cells results in a transient hyperpolarization followed by prolonged cell depolarization. Injection of inositol 1,4,5-trisphosphate or Ca2+ into the cytoplasm of NG108-15 cells also elicits cell hyperpolarization followed by depolarization. Tetraethylammonium ions inhibit the hyperpolarizing response of cells to bradykinin or inositol 1,4,5-trisphosphate. Thus, the hyperpolarizing phase of the cell response may be due to inositol 1,4,5-trisphosphate-dependent release of stored Ca2+ into the cytoplasm, which activates Ca2+-dependent K+ channels. The depolarizing phase of the cell response to bradykinin is due largely to inhibition of M channels, thereby decreasing the rate of K+ efflux from cells and, to a lesser extent, to activation of Ca2+-dependent ion channels and Ca2+ channels. In contrast, injection of inositol 1,4,5-trisphosphate or Ca2+ into the cytosol did not alter M channel activity. Incubation of NG108-15 cells with pertussis toxin inhibits bradykinin-dependent cell hyperpolarization and depolarization. Bradykinin stimulates low Km GTPase activity and inhibits adenylate cyclase in NG108-15 membrane preparations but not in membranes prepared from cells treated with pertussis toxin. Reconstitution of NG108-15 membranes from cells treated with pertussis toxin with nanomolar concentrations of a mixture of highly purified No and Ni [guanine nucleotide-binding proteins that have no known function (No) or inhibit adenylate cyclase (Ni)] restores bradykinin-dependent activation of GTPase and inhibition of adenylate cyclase. These results show that [bradykinin . receptor] complexes interact with No or Ni and suggest that No and/or Ni mediate the transduction of signals from bradykinin receptors to phospholipase C and adenylate cyclase.
authors.forename: H
authors.initials: H
authors.lastname: Higashida
authors.forename: R A
authors.initials: RA
authors.lastname: Streaty
authors.forename: W
authors.initials: W
authors.lastname: Klee
authors.forename: M
authors.initials: M
authors.lastname: Nirenberg
mesh_terms: D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D002460:Cell Line; D004075:Diglycerides / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D005910:Glioma / Q000503:physiopathology*; D006801:Humans; D006822:Hybrid Cells / Q000502:physiology; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects*; D009447:Neuroblastoma / Q000503:physiopathology*; D037342:Pertussis Toxin; D013403:Sugar Phosphates / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D004075:Diglycerides; D007295:Inositol Phosphates; D013403:Sugar Phosphates; D013757:Tetraethylammonium Compounds; D010566:Virulence Factors, Bordetella; D019789:Tetraethylammonium; D015544:Inositol 1,4,5-Trisphosphate; C038237:1-oleoyl-2-acetylglycerol; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D013755:Tetradecanoylphorbol Acetate; D001920:Bradykinin; D002118:Calcium