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INTEGRATIVE |
1 Greater Los Angeles Veterans Affairs Healthcare System
2 Department of Medicine, School of Medicine
3 Department of Biomathematics, University of California Los Angeles
4 Brentwood Biomedical Research Institute
5 Harvard-Westlake School, Los Angeles, CA 90073, USA
6 Stable Isotope Facility, Harbour UCLA Medical Center, CA 90509, USA
7 Laboratorio di Chimica Bioinorganica, Dipartimento di Chimica, Università di Firenze, Firenze, Italy
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 PCO2 with or without a cell-permeant CA inhibitor methazolamide (MTZ) or impermeant CA inhibitors. Flow-through pH and PCO2 electrodes simultaneously measured perfusate and effluent pH and PCO2. High CO2 (34.7 kPa) perfusion increased net CO2 loss from the perfusate compared with controls (pH 6.4 saline, PCO2
0) accompanied by portal venous (PV) acidification and PCO2 increase. Impermeant CA inhibitors abolished net perfusate CO2 loss and increased net HCO3– gain, whereas all CA inhibitors inhibited PV acidification and PCO2 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 PCO2 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.
(Received 14 February 2006;
accepted after revision 21 March 2006;
first published online 31 March 2006)
Corresponding author J. D. Kaunitz, Bldg 114, Suite 217, West Los Angeles VA Medical Center, 11301 Wilshire Blvd, Los Angeles, CA 90073, USA. Email jake{at}ucla.edu
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Y. Akiba, M. Mizumori, P. H. Guth, E. Engel, and J. D. Kaunitz Duodenal brush border intestinal alkaline phosphatase activity affects bicarbonate secretion in rats Am J Physiol Gastrointest Liver Physiol, December 1, 2007; 293(6): G1223 - G1233. [Abstract] [Full Text] [PDF]
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