title: A role for protein kinase C in bradykinin-mediated activation of renal pelvic sensory receptors.
abstract: In anesthetized rats, activation of renal pelvic sensory receptors by bradykinin results in an increase in afferent renal nerve activity (ARNA) that is dependent on intact renal prostaglandin synthesis. Since bradykinin is a known activator of the phosphoinositide system, we examined whether the increase in ARNA produced by bradykinin involved activation of protein kinase C (PKC). Renal pelvic perfusion with the phorbol ester 4 beta-phorbol 12,13-dibutyrate (PDBu, 1 microM) increased ARNA (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 microM), staurosporine (20 nM), and H-7 (40 microM) reduced the ARNA responses to bradykinin (20 microM) by 69 +/- 10, 76 +/- 10, and 77 +/- 10%, respectively (all P < 0.01). Pretreatment with PDBu (1 microM), known to cause a feedback inhibition of bradykinin-mediated activation of the phosphoinositide system, reduced the ARNA response to bradykinin by 73 +/- 6% (P < 0.01). Pretreatment with 4 alpha-phorbol 12,13-didecanoate was without effect. These findings suggest that activation of PKC contributes importantly to the activation of renal pelvic sensory receptors by bradykinin, likely via release of arachidonic acid.
authors.affiliation: Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, USA.
authors.forename: U C
authors.initials: UC
authors.lastname: Kopp
authors.forename: L A
authors.initials: LA
authors.lastname: Smith
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000502:physiology*; D004789:Enzyme Activation; D007546:Isoquinolines / Q000494:pharmacology; D007682:Kidney Pelvis / Q000294:innervation*; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000502:physiology*; D019311:Staurosporine
chemical_list: D000470:Alkaloids; D007546:Isoquinolines; D009281:Naphthalenes; D010879:Piperazines; D015240:Phorbol 12,13-Dibutyrate; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D019311:Staurosporine; C058819:calphostin C; D001920:Bradykinin