A ROLE FOR PROTEIN-KINASE-C IN BRADYKININ-MEDIATED ACTIVATION OF RENAL PELVIC SENSORY RECEPTORS

In anesthetized rats, activation of renal pelvic sensory receptors by bradykinin results in an increase in afferent renal nerve activity (AR NA) that is dependent on intact renal prostaglandin synthesis. Since b radykinin is a known activator of the phosphoinositide system, we exam ined whether the increase in ARNA produced by bradykinin involved acti vation of protein kinase C (PKC). Renal pelvic perfusion with the phor bol ester 4 beta-phorbol 12,13-dibutyrate (PDBu, 1 mu M) increased ARN A (31 +/- 3%, P < 0.01) in rats fed a normal diet but not in rats fed an essential fatty acid-deficient (EFAD) diet. Renal pelvic perfusion with the PKC inhibitors calphostin C (1 mu M), staurosporine (20 nM), and H-7 (40 mu M) reduced the ARNA responses to bradykinin (20 mu M) b y 69 +/- 10, 76 +/- 10, and 77 +/- 10%, respectively (all P < 0.01). P retreatment with PDBu (1 mu M), known to cause a feedback inhibition o f bradykinin-mediated activation of the phosphoinositide system, reduc ed the ARNA response to bradykinin by 73 +/- 6% (P < 0.01). Pretreatme nt with 4 alpha-phorbol 12,13-didecanoate was without effect. These fi ndings suggest that activation of PKC contributes importantly to the a ctivation of renal pelvic sensory receptors by bradykinin, likely via release of arachidonic acid.