Regulation of ion transport by 5-hydroxytryptamine in rat colon.
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 micromol/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 Ca(2+)-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 micromol/L bumetanide (an inhibitor of the Na(+)-K(+)-2Cl- cotransporter), 200 micromol/L DIDS (an inhibitor of the Na(+)-HCO3- transporter or the Cl-/HCO3- exchanger) or both decreased the DeltaISC 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 micromol/L) totally abolished the 5-HT-induced increase in ISC, whereas 2-methyl-5-HT (100 micromol/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.
Ning
Yang
Y
Epithelial Cell Biology Research Center, Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
Zhu
Jin Xia
JX
Chan
Hsiao Chang
HC
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002034:Bumetanide / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000037:antagonists & inhibitors; D004232:Diuretics / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007473:Ion Channels / Q000037:antagonists & inhibitors; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology
D004232:Diuretics; D016166:Free Radical Scavengers; D007473:Ion Channels; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D028021:Sodium-Potassium-Chloride Symporters; D002034:Bumetanide; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D012701:Serotonin; D013779:Tetrodotoxin; D012964:Sodium; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D007213:Indomethacin