POTENTIATION OF ANGIOTENSIN-II-STIMULATED PHOSPHOINOSITIDE HYDROLYSIS, CALCIUM MOBILIZATION AND CONTRACTION OF RENAL MESANGIAL CELLS UPON DOWN-REGULATION OF PROTEIN KINASE-C

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 Kd 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. © 1990.