MASS MEASUREMENTS OF INOSITOL 1,4,5-TRISPHOSPHATE AND INOSITOL 1,3,4,5-TETRAKISPHOSPHATE IN A NEURONAL CELL-LINE STIMULATED WITH BRADYKININ - INOSITOLPHOSPHATE RESPONSE SHOWS DESENSITIZATION

In a neuronal cell line (108CC15, NG108-15) the levels of inositol 1,4,5-trisphosphate (InsP3) and inositol 1,3,4,5-tetrakisphosphate (InsP4), as measured by receptor binding assays, rise transiently after stimulation with bradykinin (EC50 approx. 150 nM). Maximal InsP3 level 354 pmol/mg protein (15-fold basal level) is obtained at 10 - 15 s after addition of bradykinin, the InsP4 level rises maximally to 78 pmol/mg protein (14-fold basal level) at 20 - 30 s. In a rat glioma cell line, bradykinin (2 μM) causes a fast 6-fold increase in InsP3 and InsP4 levels. In the neuronal cells the bradykinin-dependent rise of the inositolphosphate levels is diminished with reduced extracellular Ca2+ concentration. However, depletion of internal Ca2+ stores does not affect the bradykinin-induced rise in InsP3 and InsP4 levels. Homologous desensitization to bradykinin occurs in the signal transduction pathway already at the production of inositolphosphates, since after a 2 min stimulation with bradykinin the rise in cellular masses of InsP3 and InsP4, inducible by a following second bradykinin stimulus,is substantially reduced. © 1991.