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REGULATION OF ION TRANSPORT BY 5‐HYDROXYTRYPTAMINE IN RAT COLON
Author(s) -
Ning Yang,
Zhu Jin Xia,
Chan Hsiao Chang
Publication year - 2004
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2004.04015.x
Subject(s) - dids , bumetanide , chemistry , channel blocker , cystic fibrosis transmembrane conductance regulator , glibenclamide , endocrinology , cotransporter , medicine , ion transporter , niflumic acid , biochemistry , sodium , biology , calcium , organic chemistry , membrane , diabetes mellitus , gene
SUMMARY 1. 5‐Hydroxytryptamine (5‐HT) modulates the motility and secretion of the gastrointestinal tract. To examine the direct effect of 5‐HT on the secretions of colonic epithelial cells, a short‐circuit current was used to measure electrolyte transport in the rat stripped distal colon. A neuronal Na + channel blocker and a cyclo‐oxygenase inhibitor were routinely added in experiments to abolish the effects of the enteric nervous system and endogenous prostaglandin, respectively. 2. Basolateral application of 5‐HT (10 µmol/L) induced an increase in the short circuit current ( I SC ). Removal of extracellular Cl – , HCO 3 – or both resulted in a 59.6, 76.4 and 90% reduction of 5‐HT‐elicited responses, respectively. The Ca 2+ ‐dependent Cl – channel blocker 4,4′‐diisothiocyanatostilbene‐2,2′‐disulphonic acid (DIDS) had no effect on the 5‐HT‐induced increase in I SC , but the selective cystic fibrosis transmembrane conductance regulator (CFTR) channel blocker glibenclamide (1 mmol/L) inhibited 5‐HT‐induced increases in I SC by approximately 92.9%. Removal of apical Na + reduced the 5‐HT‐induced increase in I SC by 33.3%. 3. Basolateral pretreatment with 100 µmol/L bumetanide (an inhibitor of the Na + –K + −2Cl – cotransporter), 200 µmol/L DIDS (an inhibitor of the Na + –HCO 3 – transporter or the Cl – /HCO 3 – exchanger) or both decreased the Δ I SC induced by 5‐HT by approximately 75.5, 59.0 and 86.3%, respectively. Removal of basolateral Na + also reduced the current evoked by 5‐HT. 4. The selective 5‐HT 4 antagonist GR113808 (1 µmol/L) totally abolished the 5‐HT‐induced increase in I SC , whereas 2‐methyl‐5‐HT (100 µmol/L) induced a weak I SC response . 5. In conclusion, the present study has demonstrated that 5‐HT can elicit Cl – ‐ and HCO 3 – anion secretion and Na + absorption by acting directly on colonic epithelial cells via 5‐HT 4 receptors.