2-aminoethoxydiphenyl borate stimulates pulmonary C neurons via the activation of TRPV channels

Am J Physiol Lung Cell Mol Physiol. 2005 May;288(5):L932-41. doi: 10.1152/ajplung.00439.2004. Epub 2005 Jan 14.

Abstract

This study was carried out to determine the effect of 2-aminoethoxydiphenyl borate (2-APB), a common activator of transient receptor potential vanilloid (TRPV) type 1, 2, and 3 channels, on cardiorespiratory reflexes, pulmonary C fiber afferents, and isolated pulmonary capsaicin-sensitive neurons. In anesthetized, spontaneously breathing rats, intravenous bolus injection of 2-APB elicited the pulmonary chemoreflex responses, characterized by apnea, bradycardia, and hypotension. After perineural treatment of both cervical vagi with capsaicin to block the conduction of C fibers, 2-APB no longer evoked any of these reflex responses. In open-chest and artificially ventilated rats, 2-APB evoked an abrupt and intense discharge in vagal pulmonary C fibers in a dose-dependent manner. The stimulation of C fibers by 2-APB was attenuated but not abolished by capsazepine, a selective antagonist of the TRPV1, which completely blocked the response to capsaicin in these C fiber afferents. In isolated pulmonary capsaicin-sensitive neurons, 2-APB concentration dependently evoked an inward current that was partially inhibited by capsazepine but almost completely abolished by ruthenium red, an effective blocker of all TRPV channels. In conclusion, 2-APB evokes a consistent and distinct stimulatory effect on pulmonary C fibers in vivo and on isolated pulmonary capsaicin-sensitive neurons in vitro. These results establish the functional evidence demonstrating that TRPV1, V2, and V3 channels are expressed on these sensory neurons and their terminals.

Publication types

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

MeSH terms

  • Animals
  • Blood Pressure / drug effects
  • Boron Compounds / pharmacology*
  • Capsaicin / analogs & derivatives*
  • Capsaicin / pharmacology
  • Cation Transport Proteins / physiology
  • Coloring Agents / pharmacology
  • Heart Rate / drug effects
  • Ion Channels / physiology*
  • Lung / innervation*
  • Nerve Fibers, Unmyelinated / drug effects*
  • Nerve Fibers, Unmyelinated / physiology*
  • Nodose Ganglion / cytology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Drug / physiology
  • Reflex / drug effects
  • Respiratory Mechanics / drug effects
  • Ruthenium Red / pharmacology
  • TRPV Cation Channels

Substances

  • Boron Compounds
  • Cation Transport Proteins
  • Coloring Agents
  • Ion Channels
  • Receptors, Drug
  • TRPV Cation Channels
  • Trpv1 protein, rat
  • Trpv2 protein, rat
  • Trpv3 protein, mouse
  • Ruthenium Red
  • 2-aminoethoxydiphenyl borate
  • capsazepine
  • Capsaicin