Preferential activation of the vagal nodose nociceptive subtype by TRPA1 agonists in the guinea pig esophagus

M. Brozmanova, F. Ru, L. Surdenikova, L. Mazurova, T. Taylor-Clark, M. Kollarik

Research output: Contribution to journalArticle

Abstract

Background The TRPA1 receptor is directly activated by a wide range of chemicals including many endogenous molecules relevant for esophageal pathophysiology. We addressed the hypothesis that the TRPA1 agonists differentially activate esophageal nociceptive subtypes depending on their embryological source (neural crest or epibranchial placodes). Methods Single cell RT-PCR and whole cell patch clamp recordings were performed on the vagal neurons retrogradely labeled from the guinea pig esophagus. Extracellular recordings were made in the isolated innervated esophagus preparation ex vivo. Key Results Single cell RT-PCR revealed that the majority of the nodose (placodes-derived) and jugular (neural crest-derived) TRPV1-positive esophageal nociceptors express TRPA1. Single fiber recording showed that the TRPA1 agonists allyl-isothiocyanate (AITC) and cinnamaldehyde were effective in inducing robust action potential discharge in the nerve terminals of nodose nociceptors, but had far less effect in jugular nociceptors (approximately fivefold less). Higher efficacy of the TRPA1 agonists to activate nodose nociceptors was confirmed in the isolated esophagus-labeled vagal neurons in the whole cell patch clamp studies. Similarly to neural crest-derived vagal jugular nociceptors, the spinal DRG nociceptors that are also neural crest-derived were only modestly activated by allyl-isothiocyanate. Conclusions & Inferences We conclude that the TRPA1 agonists are substantially more effective activators of the placodes-derived than the neural crest-derived esophageal nociceptors. Our data predict that in esophageal diseases the presence of endogenous TRPA1 activators will be preferentially signaled by the vagal nodose nociceptors.

Original languageEnglish (US)
Pages (from-to)e437-e445
JournalNeurogastroenterology and Motility
Volume23
Issue number10
DOIs
StatePublished - Oct 1 2011

ASJC Scopus subject areas

  • Physiology
  • Endocrine and Autonomic Systems
  • Gastroenterology

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