Activation of renal mechanosensitive neurons involves bradykinin, protein kinase C, PGE(2), and substance P

Am J Physiol Regul Integr Comp Physiol. 2000 Apr;278(4):R937-46. doi: 10.1152/ajpregu.2000.278.4.R937.

Abstract

Increased renal pelvic pressure or bradykinin increases afferent renal nerve activity (ARNA) via PGE(2)-induced release of substance P. Protein kinase C (PKC) activation increases ARNA, and PKC inhibition blocks the ARNA response to bradykinin. We now examined whether bradykinin mediates the ARNA response to increased renal pelvic pressure by activating PKC. In anesthetized rats, the ARNA responses to increased renal pelvic pressure were blocked by renal pelvic perfusion with the bradykinin B(2)-receptor antagonist HOE 140 and the PKC inhibitor calphostin C by 76 +/- 8% (P < 0.02) and 81 +/- 5% (P < 0.01), respectively. Renal pelvic perfusion with 4beta-phorbol 12,13-dibutyrate (PDBu) to activate PKC increased ARNA 27 +/- 4% and renal pelvic release of PGE(2) from 500 +/- 59 to 1, 113 +/- 183 pg/min and substance P from 10 +/- 2 to 30 +/- 2 pg/min (all P < 0.01). Indomethacin abolished the increases in substance P release and ARNA. The PDBu-mediated increase in ARNA was also abolished by the substance P-receptor antagonist RP 67580. We conclude that bradykinin contributes to the activation of renal pelvic mechanosensitive neurons by activating PKC. PKC increases ARNA via a PGE(2)-induced release of substance P.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology
  • Analgesics / pharmacology
  • Animals
  • Antimetabolites / pharmacology
  • Bradykinin / analogs & derivatives
  • Bradykinin / metabolism*
  • Bradykinin / pharmacology
  • Bradykinin Receptor Antagonists
  • Cyclooxygenase Inhibitors / pharmacology
  • Dinoprostone / metabolism*
  • Enzyme Activation / drug effects
  • Enzyme Activation / physiology
  • Enzyme Inhibitors / pharmacology
  • Indoles / pharmacology
  • Isoindoles
  • Kidney / innervation*
  • Kidney Pelvis / physiology
  • Male
  • Mechanoreceptors / physiology*
  • Naphthalenes / pharmacology
  • Natriuresis / physiology
  • Neurokinin-1 Receptor Antagonists
  • Neurons, Afferent / chemistry
  • Neurons, Afferent / drug effects
  • Neurons, Afferent / enzymology*
  • Phorbol 12,13-Dibutyrate / pharmacology
  • Pressure
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Bradykinin B2
  • Receptors, Bradykinin / metabolism
  • Receptors, Neurokinin-1 / metabolism
  • Substance P / metabolism*

Substances

  • Adrenergic beta-Antagonists
  • Analgesics
  • Antimetabolites
  • Bradykinin Receptor Antagonists
  • Cyclooxygenase Inhibitors
  • Enzyme Inhibitors
  • Indoles
  • Isoindoles
  • Naphthalenes
  • Neurokinin-1 Receptor Antagonists
  • Receptor, Bradykinin B2
  • Receptors, Bradykinin
  • Receptors, Neurokinin-1
  • calphostin complex
  • 7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one
  • Substance P
  • Phorbol 12,13-Dibutyrate
  • icatibant
  • Protein Kinase C
  • Dinoprostone
  • Bradykinin