Carbonic Anhydrases and Mucosal Vanilloid Receptors Help Mediate the Hyperemic Response to Luminal CO2 in Rat Duodenum

CFTR inhibition augments NHE3 activity during luminal high CO2exposure in rat duodenal mucosa

“…Furthermore, CFTR inhibition prevented CO2-induced cellular acidification reversed by S3226. Reversal of increased HCO 3 Ϫ loss by NHE3 inhibition and reduced intracellular acidification during CFTR inhibition is consistent with activation or unmasking of NHE3 activity by CFTR inhibition, increasing cell surface H ϩ available to neutralize luminal HCO 3 Ϫ with consequent CO2 absorption. NHE3, by secreting H ϩ into the luminal microclimate, facilitates net transmucosal HCO 3 Ϫ absorption with a mechanism similar to proximal tubular HCO 3 Ϫ absorption.…”

“…One of the unexplained mysteries of duodenal HCO 3 Ϫ secretion is why it is needed, given that secretion into the lumen from pancreas and liver is more than adequate to fully neutralize the bulk luminal content (13). Epithelial HCO 3 Ϫ secretion has thus been hypothesized to neutralize a distinct "preepithelial layer" adjacent to the apical plasma membrane of the mucosa (10,24). Moreover, the upper intestine absorbs HCO 3 Ϫ by an electroneutral Na ϩ -dependent mechanism, hypothesized to be Na ϩ /H ϩ exchange (37).…”

“…Epithelial HCO 3 Ϫ secretion has thus been hypothesized to neutralize a distinct "preepithelial layer" adjacent to the apical plasma membrane of the mucosa (10,24). Moreover, the upper intestine absorbs HCO 3 Ϫ by an electroneutral Na ϩ -dependent mechanism, hypothesized to be Na ϩ /H ϩ exchange (37). Since the epithelial Na ϩ /H ϩ exchanger (NHE) 3, which helps facilitate intestinal neutral NaCl absorption, is highly expressed in duodenum (31), we wondered whether duodenal NHE3 additionally functions as an H ϩ secretor, as it does in the proximal tubule (33, 38), facilitating HCO 3 Ϫ absorption.…”

“…Moreover, the upper intestine absorbs HCO 3 Ϫ by an electroneutral Na ϩ -dependent mechanism, hypothesized to be Na ϩ /H ϩ exchange (37). Since the epithelial Na ϩ /H ϩ exchanger (NHE) 3, which helps facilitate intestinal neutral NaCl absorption, is highly expressed in duodenum (31), we wondered whether duodenal NHE3 additionally functions as an H ϩ secretor, as it does in the proximal tubule (33, 38), facilitating HCO 3 Ϫ absorption. The duodenum must also absorb ϳ450 mmol of gastric H ϩ /24 h to decrease luminal hydrogen concentration ([H ϩ ]) by 6 log orders over its 15-cm length (12).…”

The Role of Capsaicin-Sensitive Afferent Nerves in Gastric Mucosal Protection Initiated Centrally or Peripherally under Experimental Conditions

“…The acid-evoked hyperemia in the esophageal and duodenal mucosa is inhibited by the TRPV1 antagonist capsazepine or sensory denervation, suggesting that acid activates TRPV1 on sensory nerve fibers [85,86]. As a result, activation of TRPV1-positive sensory nerve fibers are able to protect the esophageal, gastric and intestinal mucosa from a variety of injurious by stimulating mucosal microcirculation [61].…”