REGULATION OF ION TRANSPORT BY 5-HYDROXYTRYPTAMINE IN RAT COLON

Authors

  • Yang Ning,

    1. Epithelial Cell Biology Research Center, Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong and
    2. Department of Physiology, Medical School, Zhengzhou University, Zhengzhou, Henan, PR China
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  • Jin Xia Zhu,

    1. Epithelial Cell Biology Research Center, Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong and
    2. Department of Physiology, Medical School, Zhengzhou University, Zhengzhou, Henan, PR China
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  • Hsiao Chang Chan

    1. Epithelial Cell Biology Research Center, Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong and
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Professor HC Chan, Epithelial Cell Biology Research Center, Department of Physiology, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, SAR. Email: hsiaocchan@cuhk.edu.hk

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 (ISC). Removal of extracellular Cl, HCO3 or both resulted in a 59.6, 76.4 and 90% reduction of 5-HT-elicited responses, respectively. The Ca2+-dependent Cl channel blocker 4,4′-diisothiocyanatostilbene-2,2′-disulphonic acid (DIDS) had no effect on the 5-HT-induced increase in ISC, but the selective cystic fibrosis transmembrane conductance regulator (CFTR) channel blocker glibenclamide (1 mmol/L) inhibited 5-HT-induced increases in ISC by approximately 92.9%. Removal of apical Na+ reduced the 5-HT-induced increase in ISC 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+–HCO3 transporter or the Cl/HCO3 exchanger) or both decreased the ΔISC 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-HT4 antagonist GR113808 (1 µmol/L) totally abolished the 5-HT-induced increase in ISC, whereas 2-methyl-5-HT (100 µmol/L) induced a weak ISC response.

5. In conclusion, the present study has demonstrated that 5-HT can elicit Cl- and HCO3 anion secretion and Na+ absorption by acting directly on colonic epithelial cells via 5-HT4 receptors.

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