NHE3 inhibition activates duodenal bicarbonate secretion in the rat
| Autor: | Eli Engel, Osamu Furukawa, Luke C. Bi, Jonathan D. Kaunitz, Paul H. Guth, Masahiko Hirokawa |
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| Rok vydání: | 2003 |
| Předmět: |
Male
medicine.medical_specialty Sodium-Hydrogen Exchangers Physiology Duodenum Bicarbonate Indomethacin Methazolamide 4 4'-Diisothiocyanostilbene-2 2'-Disulfonic Acid Guanidines Amiloride Rats Sprague-Dawley chemistry.chemical_compound Physiology (medical) Internal medicine medicine Image Processing Computer-Assisted Animals Secretion Enzyme Inhibitors Carbonic Anhydrase Inhibitors Nitrobenzenes Hepatology biology urogenital system Sodium-Hydrogen Exchanger 3 Anti-Inflammatory Agents Non-Steroidal Gastroenterology Carbon Dioxide Hydrogen-Ion Concentration Epithelium Cystic fibrosis transmembrane conductance regulator Rats Sprague dawley Back titration Bicarbonates medicine.anatomical_structure Endocrinology chemistry biology.protein Methacrylates Cytophotometry |
| Zdroj: | American journal of physiology. Gastrointestinal and liver physiology. 286(1) |
| ISSN: | 0193-1857 |
| Popis: | We examined the effect of inhibition of Na+/H+exchange (NHE) on duodenal bicarbonate secretion (DBS) in rats to further understand DBS regulation. DBS was measured by using the pH-stat method and by using CO2-sensitive electrodes. 5-( N,N-dimethyl)-amiloride (50 μM; DMA), a concentration that selectively inhibits the NHE isoforms NHE1 and NHE2, but not NHE3, did not affect DBS. Nevertheless, 3 mM DMA, a higher concentration that inhibits NHE1, NHE2, and NHE3, significantly increased DBS. Moreover, S1611 and S3226, both specific inhibitors of NHE3 only, or perfusion with Na+-free solutions, dose dependently increased DBS, as measured by pH-stat and CO2-sensitive electrode, without affecting intracellular pH. Coperfusion with 0.1 μM indomethacin, 0.5 mM DIDS, or 1 mM methazolamide did not affect S3226-induced DBS. Nevertheless, coperfusion with 0.1 and 0.3 mM 5-nitro-2-(3-phenylpropylamino) benzoic acid, which inhibits the cystic fibrosis transmembrane conductor regulator (CFTR), dose dependently inhibited S3226-induced DBS. In conclusion, only specific apical NHE3 inhibition increased DBS, whereas prostaglandin synthesis, [Formula: see text] cotransporter activation, or intracellular [Formula: see text] formation by carbonic anhydrase was not involved. Because NHE3 inhibition-increased DBS was inhibited by an anion channel inhibitor and because reciprocal CFTR regulation has been previously shown between NHE3 and apical membrane anion transporters, we speculate that NHE3 inhibition increased DBS by altering anion transporter function. |
| Databáze: | OpenAIRE |
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