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Tumour promotor 12‐ O ‐tetradecanoylphorbol 13‐acetate inhibits angiotensin II‐induced inositol phosphate production and cytosolic Ca 2+ rise in rat renal mesangial cells
Author(s) -
Pfeilschifter Josef
Publication year - 1986
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(86)80755-4
Subject(s) - protein kinase c , angiotensin ii , cytosol , inositol phosphate , inositol , chemistry , medicine , endocrinology , mesangial cell , receptor , inositol trisphosphate , phospholipase c , kinase , biochemistry , in vitro , biology , enzyme
Preincubation of rat renal mesangial cells with 12‐ O ‐tetradecanoylphorbol 13‐acetate (TPA) strongly inhibited the increases of inositol phosphates and of free cytosolic Ca 2+ induced by angiotensin II (10 −7 M). TPA had no significant effect on the basal values of inositol phosphates and of free cytosolic Ca 2+ . Inhibition appeared already after 1 min and was maximal after 5 min. These effects occur without significant changes on angiotensin II binding in intact cells. The concentration of TPA needed (10 −9 –10 −7 M) was in the range believed to cause specifically an activation of protein kinase C. Furthermore the biologically inactive phorbol ester 4α‐phorbol 12,13‐didecanoate was without effect. From the entirety of these results it is likely that protein kinase C inhibits angiotensin II activation of phospholipase C at a stage distal to receptor occupancy.