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Luminal 5‐HT induces HCO 3 ‐ secretion via 5‐HT4 in rat proximal colon (1181.11)
Author(s) -
Kaji Izumi,
Akiba Yasutada,
Kaunitz Jonathan
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1181.11
Subject(s) - 5 ht4 receptor , enterochromaffin cell , medicine , chemistry , endocrinology , secretion , agonist , tetrodotoxin , serotonin , ussing chamber , receptor , biology
5‐hydroxytryptamine (5‐HT), contained in enterochromaffin cells, is abundantly produced throughout the gastrointestinal tract. 5‐HT is released into the gut lumen and into the submucosa, although reports of its luminal activity and function, with particular reference to ion transport, are infrequent. In rat proximal colon, short‐circuit current (Isc), as measured in Ussing‐chambered mucosa‐submucosa preparations, was gradually increased to a sustained value following the luminal application of 5‐HT (10 ‐ 100 μM). Increasing in Isc was NKCC1‐independent but carbonic anhydrase‐dependent, consistent with electrogenic HCO3‐ secretion. The neurotoxin tetrodotoxin (TTX) or cyclooxygenase (COX) inhibitor indomethacin did not alter the response to luminal 5‐HT. Pretreatment with forskolin abolished the response to luminal 5‐HT, indicating that cAMP mediates 5‐HT‐induced ion secretion. Luminal pretreatment with the 5‐HT4 receptor antagonist GR113808 (1 μM), but not with 5‐HT2 or 5‐HT6 antagonists, inhibited the response to luminal 5‐HT, whereas serosal GR113808 had no effect. Furthermore, the luminal 5‐HT4 agonist cisapride increased Isc to the same extent as did 5‐HT. These results suggest that a novel mucosal 5‐HT4‐mediated HCO3‐ secretory pathway is present in the colon. Luminal 5‐HT4 may be important in the maintenance of luminal pH and pCO2, while preserving adequate luminal fluid volume. Grant Funding Source : VA Merit Review, NIH R01 DK54221, JSPS