Bradykinin-activated transmembrane signals are coupled via N/sub o/ or N/sub i/ to production of inositol 1,4,5-trisphosphate, a second messenger in NG108-15 neuroblastoma-glioma hybrid cells
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 CaS 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 UVCa-labelled CaS into the cytoplasm, which activates CaS -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 CaS -dependent ion channels and CaS channels. In contrast, injection of inositol 1,4,5-trisphosphate or CaS 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 K/sub m/ GTPase activity and inhibits adenylate cyclase in NG108-15 membrane preparations but not in membranes prepared from cells treated with pertussis toxin. These results show that (bradykinin-receptor) complexes interact with N/sub o/ or N/sub i/ and suggest that N/sub o/ and/or N/sub i/ mediate the transduction of signals from bradykinin receptors to phospholipase C and adenylate cyclase.
- Research Organization:
- National Institutes of Health (NIH), Bethesda, MD (United States)
- OSTI ID:
- 6415710
- Journal Information:
- Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 83:4
- Country of Publication:
- United States
- Language:
- English
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CALCIUM 45
UPTAKE
MEMBRANE TRANSPORT
CHEMICAL ACTIVATION
TUMOR CELLS
ELECTRIC POTENTIAL
BIOELECTRICITY
BRADYKININ
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CYCLASES
INOSITOLS
TEAB
TOXINS
ALKALINE EARTH ISOTOPES
ALKALINE EARTH METAL COMPOUNDS
AMINES
AMMONIUM COMPOUNDS
ANIMAL CELLS
ANTIGENS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BROMIDES
BROMINE COMPOUNDS
CALCIUM COMPOUNDS
CALCIUM HALIDES
CALCIUM ISOTOPES
CARBOHYDRATES
CHLORIDES
CHLORINE COMPOUNDS
DAYS LIVING RADIOISOTOPES
ELECTRICITY
ENZYMES
EVEN-ODD NUCLEI
HALIDES
HALOGEN COMPOUNDS
INTERMEDIATE MASS NUCLEI
ISOTOPES
KININS
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MATERIALS
MONOSACCHARIDES
NUCLEI
ORGANIC COMPOUNDS
PEPTIDES
POLYPEPTIDES
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TOXIC MATERIALS
550201* - Biochemistry- Tracer Techniques