2-aminoethoxydiphenyl borate stimulates pulmonary C neurons via the activation of TRPV channels.
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.
Gu
Qihai
Q
Dept. of Physiology, University of Kentucky Medical Center, Lexington, KY 40536-0298, USA.
Lin
Ruei-Lung
RL
Hu
Hong-Zhen
HZ
Zhu
Michael X
MX
Lee
Lu-Yuan
LY
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001896:Boron Compounds / Q000494:pharmacology*; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D027682:Cation Transport Proteins / Q000502:physiology; D004396:Coloring Agents / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007473:Ion Channels / Q000502:physiology*; D008168:Lung / Q000294:innervation*; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects* / Q000502:physiology*; D009620:Nodose Ganglion / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000502:physiology; D012018:Reflex / Q000187:drug effects; D015656:Respiratory Mechanics / Q000187:drug effects; D012430:Ruthenium Red / Q000494:pharmacology; D050916:TRPV Cation Channels
D001896:Boron Compounds; D027682:Cation Transport Proteins; D004396:Coloring Agents; D007473:Ion Channels; D011955:Receptors, Drug; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C476722:Trpv2 protein, rat; C486760:Trpv3 protein, mouse; D012430:Ruthenium Red; C109986:2-aminoethoxydiphenyl borate; C071423:capsazepine; D002211:Capsaicin