Differential effects of transient receptor vanilloid one (TRPV1) antagonists in acid-induced excitation of esophageal vagal afferent fibers of rats. Neuroscience 2009 Jun 30;161(2):515-25
Date
03/28/2009Pubmed ID
19324074Pubmed Central ID
PMC2703792DOI
10.1016/j.neuroscience.2009.03.040Scopus ID
2-s2.0-67349124372 (requires institutional sign-in at Scopus site) 36 CitationsAbstract
Gastro-esophageal acid reflux can stimulate esophageal vagal sensory afferents by activating proton-sensitive ion channel transient receptor vanilloid one (TRPV1). The objective of this study was to investigate the response characteristics of vagal afferent fibers of rats to acid (0.1 N HCl) and capsaicin (CAP) following esophagitis and differential effects of two classes of TRPV1 antagonists on responses of vagal afferent fibers. The chronic reflux was induced by ligating the fundus of the stomach and partial constriction of pylorus. Extracellular single fiber recordings were made from the cervical vagal afferent fibers from naive control and fundus-ligated (FL) esophagitis rats. Innervations of fibers were identified to esophageal distension (ED) and subsequently tested to CAP and acid before and after injection of TRPV1 antagonist JYL1421 or AMG9810 (10 micromol/kg i.v.). Seventy-five vagal afferent fibers from 70 rats were identified to ED. Intra-esophageal CAP (0.1 ml of 1 mg/ml) excited 39.5% (17/43, 5/22 from naive and 12/21 from FL rats) fibers. In contrast, i.v. injection of CAP (0.03-0.3 micromol/kg) dose-dependently excited 72% (42/58) fibers. Responses to CAP were significantly greater for fibers from FL rats (n=32) than naive rats (n=25). TRPV1 antagonists JYL1421 and AMG9810 (10 micromol/kg) significantly blocked response to CAP. Intra-esophageal acid infusion stimulated 5/17 (29.4%) fibers from naive rats and 12/28 (42%) from FL rats. Effect of acid was significantly blocked by AMG9810, but not by JYL1421. Results indicate that following esophagitis the number of fibers responsive to CAP and acid is greater than noninflamed esophagus, which may contribute to esophageal hypersensitivity. Acid-induced excitation of vagal sensory afferents can be differentially attenuated by different classes of TRPV1 antagonists. Therefore, TRPV1 antagonists play a key role in attenuation of hypersensitivity following reflux-induced esophagitis. The use of TRPV1 antagonists could be an alternative to the traditional symptoms-based treatment of chronic acid reflux and esophageal hypersensitivity.
Author List
Peles S, Medda BK, Zhang Z, Banerjee B, Lehmann A, Shaker R, Sengupta JNAuthors
Banani Banerjee PhD Associate Professor in the Medicine department at Medical College of WisconsinBidyut K. Medda PhD Associate Professor in the Medicine department at Medical College of Wisconsin
Jyoti N. Sengupta PhD Professor in the Medicine department at Medical College of Wisconsin
Reza Shaker MD Assoc Provost, Sr Assoc Dean, Ctr Dir, Chief, Prof in the Medicine department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AcrylamidesAfferent Pathways
Animals
Bridged Bicyclo Compounds, Heterocyclic
Capsaicin
Chronic Disease
Esophagitis, Peptic
Esophagus
Hydrochloric Acid
Hydrogen-Ion Concentration
Male
Mechanotransduction, Cellular
Nerve Fibers
Rats
Rats, Sprague-Dawley
Sulfonamides
TRPV Cation Channels
Thiourea
Vagus Nerve
