Epithelial carbonic anhydrases facilitate PCO2 and pH regulation in rat duodenal mucosa

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Abstract
The duodenum is the site of mixing of massive amounts of gastric H+ with secreted HCO3−, generating CO2 and H2O accompanied by the neutralization of H+. We examined the role of membrane‐bound and soluble carbonic anhydrases (CA) by which H+ is neutralized, CO2 is absorbed, and HCO3− is secreted. Rat duodena were perfused with solutions of different pH and P with or without a cell‐permeant CA inhibitor methazolamide (MTZ) or impermeant CA inhibitors. Flow‐through pH and P electrodes simultaneously measured perfusate and effluent pH and P . High CO2 (34.7 kPa) perfusion increased net CO2 loss from the perfusate compared with controls (pH 6.4 saline, P≈ 0) accompanied by portal venous (PV) acidification and P increase. Impermeant CA inhibitors abolished net perfusate CO2 loss and increased net HCO3− gain, whereas all CA inhibitors inhibited PV acidification and P increase. The changes in luminal and PV pH and [CO2] were also inhibited by the Na+–H+ exchanger‐1 (NHE1) inhibitor dimethylamiloride, but not by the NHE3 inhibitor S3226. Luminal acid decreased total CO2 output and increased H+ loss with PV acidification and P increase, all inhibited by all CA inhibitors. During perfusion of a 30% CO2 buffer, loss of CO2 from the lumen was CA dependent as was transepithelial transport of perfused 13CO2. H+ and CO2 loss from the perfusate were accompanied by increases of PV H+ and tracer CO2, but unchanged PV total CO2, consistent with CA‐dependent transmucosal H+ and CO2 movement. Inhibition of membrane‐bound CAs augments the apparent rate of net basal HCO3− secretion. Luminal H+ traverses the apical membrane as CO2, is converted back to cytosolic H+, which is extruded via NHE1. Membrane‐bound and cytosolic CAs cooperatively facilitate secretion of HCO3− into the lumen and CO2 diffusion into duodenal mucosa, serving as important acid–base regulators.

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