To test whether the transient receptor potential channel vanilloid subfamily member-1 (TRPV1) mediates acid-induced inflammation in the esophagus, a tubular segment of esophageal mucosa was tied at both ends, forming a sac. The sac was filled with 0.01N HCl (or Krebs for control) and kept in oxygenated Krebs at 37° C. The medium around the sac (supernatant) was collected after 3 hours. Supernatant of the HCl-filled sac abolished contraction of esophageal circular muscle strips in response to electric field stimulation. Contraction was similarly abolished by supernatant of mucosal sac filled with the TRPV1 agonist capsaicin (10^-6 M). These effects were reversed by the selective TRPV1 antagonist IRTX and by the PAF receptor antagonist CV9388. Substance P and CGRP levels in mucosa and in supernatant increased in response to HCl, and these increases were abolished by IRTX and by tetrodotoxin, but not affected by CV9388, indicating that Substance P and CGRP are neurally released and PAF independent. In contrast, the increase in PAF was blocked by IRTX but not by TTX. Presence of TRPV1 receptor was confirmed by RT-PCR and by Western blot analysis in whole mucosa and in esophageal epithelial cells enzymatically isolated, and sorted by flow cytometry or immuno-precipitated with cytokeratin antibodies. In epithelial cells PAF increased in response to HCL, and the increase was abolished by IRTX. We conclude: HCl-induced activation of TRPV1 receptors in esophageal mucosa causes release of substance P and CGRP, from neurons and release of PAF from epithelial cells.