Bradykinin-induced rapid breakdown of phosphatidylinositol 4,5-bisphosphate in neuroblastoma X glioma hybrid NG108-15 cells.
External application of bradykinin to neuroblastoma X glioma hybrid NG108-15 cells produced a sustained depolarization preceded by a transient hyperpolarization. Bradykinin also increased the frequency of miniature end-plate potentials recorded from cultured striated muscle cells which had been innervated by NG108-15 cells. Parallelism between facilitative phases of miniature end-plate potentials and depolarization indicates that bradykinin caused an enhanced synaptic transmission from NG108-15 cells due to depolarization. Effects of bradykinin on phospholipid metabolism in the hybrid cells were then examined to shed light upon the mechanism by which bradykinin-receptor interaction leads to facilitation of synaptic transmission. Bradykinin induced specific incorporation of 32Pi into phosphatidic acid and phosphatidylinositol without affecting [3H]glycerol incorporation into these phospholipids by 10 min after its addition. The addition of bradykinin to hybrid cells prelabeled with 32Pi caused a transient decrease (maximal effect seen at 10-30 s) in the radioactivity from phosphatidylinositol 4,5-bisphosphate (PI-4,5-P2) which was followed by the accumulation of radioactivity in phosphatidic acid and phosphatidylinositol. A Ca2+ ionophore, A23187, failed to induce the initial degradation of PI-4,5-P2. The data show that the magnitudes of bradykinin-induced PI-4,5-P2 degradation and membrane potential changes in NG108-15 cells are both dependent on the concentration of bradykinin and that the degradation of PI-4,5-P2 precedes the electrophysiological responses. Taken together with the finding that bradykinin induced a transient increase in Ca2+ influx (at 10-20 s), it appears that a rapid and transient degradation of PI-4,5-P2 might be related to the initiation of the NG108-15 cell activities through mobilization of extracellular Ca2+ into the cells.
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002460:Cell Line; D005910:Glioma / Q000378:metabolism / Q000503:physiopathology*; D005990:Glycerol / Q000378:metabolism; D006822:Hybrid Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism / Q000503:physiopathology*; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000378:metabolism*; D010743:Phospholipids / Q000096:biosynthesis; D051381:Rats; D009435:Synaptic Transmission / Q000187:drug effects
D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D010743:Phospholipids; D005990:Glycerol; D001920:Bradykinin