α-Thrombin-induced inositol phosphate formation in go-arrested and cycling hamster lung fibroblasts: Evidence for a protein kinase C-mediated desensitization response

摘要: In resting Chinese hamster fibroblasts (CCL39) ..cap alpha..-thrombin rapidly induces the breakdown of phosphoinositides. Accumulation inositol phosphates (IP), measured in presence Li/sup +/, is detectable within 5s (seconds) thrombin stimulation. Formation tris- and bisphosphates slightly precedes that monophosphate, indicating activates primarily phospholipase C-mediated generation trisphosphate from phosphatidylinositol 4,5-bisphosphate. Initial rates IP production increase with concentration, no apparent saturability over range 10/sup -4/-10 U/ml. Thrombin-induced phosphoinositide hydrolysis desensitizes (t/sub 1/2/ > 5 min), but a residual activity, corresponding to about 10% initial stimulation sustained for at least 9 h, contrast undetectable activity G0-arrested cells. This desensitization may be due feedback regulation by protein kinase C, since pretreatment phorbol ester 12-O-tetradecanoyl 13-acetate (TPA) markedly inhibits (by up 70%) subsequent thrombin-induced phosphate formation. was found maximal A51, very well growth-arrested CCL39 derivative,and reduced or virtually abolished two tumoral growth factor-relaxed derivatives CCL39. Although preliminary, this observation suggests persistent activation phosphatidyl might operate variants selected autonomousmore » growth.« less