Potentiation of angiotensin II‐stimulated phosphoinositide hydrolysis, calcium mobilization and contraction of renal mesangial cells upon down‐regulation of protein kinase C

Abstract

Long-term pretreatment of rat mesangial cells with 12-O-tetradecanoylphorbol 13-acetate (TPA) down-regulated protein kinase C activity and potentiated the angiotensin II-induced inositol trisphosphate (InsP₃) formation. This increased response to angiotensin II occurred without a significant change in the receptor number or K _d value of angiotensin II binding to the cells. The biologically inactive phorbol ester 4α-phorbol 12,13-di-decanoate was without effect on angiotensin II-stimulated InsP₃ generation. Long-term pretreatment with TPA also increased the angiotensin II-induced mobilization of Ca²⁺ and the subsequent contraction of mesangial cells.