Tumour promotor 12‐O‐tetradecanoylphorbol 13‐acetate inhibits angiotensin II‐induced inositol phosphate production and cytosolic Ca2+ rise in rat renal mesangial cells

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Abstract
Preincubation of rat renal mesangial cells with 12-O-tetradecanoylphorbol 13-acetate (TPA) strongly inhibited the increases of inositol phosphates and of free cytosolic Ca2+ induced by angiotensin II (10−7 M). TPA had no significant effect on the basal values of inositol phosphates and of free cytosolic Ca2+. 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.