AGI August 40/2

Akiba, Yasutada, Paul H. Guth, Eli Engel, Igor Nastaskin, and Jonathan D. Kaunitz. Acid-sensing pathways of rat duodenum. Am. J. Physiol. 277 (Gastrointest. Liver Physiol. 40): G268–G274, 1999.—We tested the hypothesis that the duodenal hyperemic response to acid occurs through activation of capsaicin-sensitive afferent nerves with subsequent release of vasodilatory substances such as calcitonin gene-related peptide (CGRP) and nitric oxide (NO). LaserDoppler flowmetry was used to measure duodenal blood flow in urethan-anesthetized rats. Duodenal mucosa was superfused with pH 7.0 buffer with capsaicin or bradykinin or was acid challenged with pH 2.2 solution, with or without vanilloid receptor antagonists, a CGRP receptor antagonist, an NO synthase (NOS) inhibitor, or a cyclooxygenase inhibitor. The selective vanilloid receptor antagonist capsazepine (CPZ) dose dependently inhibited the hyperemic response to acid and capsaicin but did not affect bradykinin-induced hyperemia. Ruthenium red was less inhibitory than capsazepine. Selective ablation of capsaicin-sensitive nerves, CGRP-(8— 37), and NG-nitro-L-arginine methyl ester inhibited acidinduced hyperemia, but indomethacin did not. We conclude that luminal acid, but not bradykinin, stimulates CPZsensitive receptors on capsaicin-sensitive afferent nerves of rat duodenum. Activation of these receptors produces vasodilation via the CGRP-NO pathway but not via the cyclooxygenase pathway. Acid appears to be the endogenous ligand for duodenal vanilloid receptors.