Stimulation of chloride secretion by baicalein in isolated rat distal colon

The effect of baicalein on mucosal ion transport in the rat distal colon was investigated in Ussing chambers. Mucosal addition of baicalein (1-100 microM) elicited a concentration-dependent short-circuit current (I(sc)) response. The increase in I(sc) was mainly due to Cl(-) secretion. The presence...

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Published in:American journal of physiology: Gastrointestinal and liver physiology 2002-03, Vol.282 (3), p.G508-G518
Main Authors: Ko, W H, Law, V W Y, Yip, W C Y, Yue, G G L, Lau, C W, Chen, Z Y, Huang, Y
Format: Article
Language:English
Subjects:
1-Methyl-3-isobutylxanthine - pharmacology
Amiloride - pharmacology
Animals
Atropine - pharmacology
Calcium - metabolism
Carbachol - pharmacology
Chlorides - metabolism
Colforsin - pharmacology
Colon - drug effects
Colon - secretion
Cyclic AMP - biosynthesis
Dinoprostone - pharmacology
Electric Conductivity
Female
Flavanones
Flavonoids - pharmacology
Indomethacin - pharmacology
Intestinal Mucosa - drug effects
Male
Muscarinic Antagonists - pharmacology
Potassium Channel Blockers
Rats
Rats, Sprague-Dawley
Tetrodotoxin - pharmacology
Thapsigargin - pharmacology
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Summary:The effect of baicalein on mucosal ion transport in the rat distal colon was investigated in Ussing chambers. Mucosal addition of baicalein (1-100 microM) elicited a concentration-dependent short-circuit current (I(sc)) response. The increase in I(sc) was mainly due to Cl(-) secretion. The presence of mucosal indomethacin (10 microM) significantly reduced both the basal and subsequent baicalein-evoked I(sc) responses. The baicalein-induced I(sc) were inhibited by mucosal application of diphenylamine-2-carboxylic acid (100 microM) and glibenclamide (500 microM) and basolateral application of chromanol 293B (30 microM), a blocker of K(v)LQT1 channels and Ba(2+) ions (5 mM). Treatment of the colonic mucosa with baicalein elicited a threefold increase in cAMP production. Pretreating the colonic mucosa with carbachol (100 microM, serosal) but not thapsigargin (1 microM, both sides) abolished the baicalein-induced I(sc). Addition of baicalein subsequent to forskolin induced a further increase in I(sc). These results indicate that the baicalein evoked Cl(-) secretion across rat colonic mucosa, possibly via a cAMP-dependent pathway. However, the action of baicalein cannot be solely explained by its cAMP-elevating effect. Baicalein may stimulate Cl(-) secretion via a cAMP-independent pathway or have a direct effect on cystic fibrosis transmembrane conductance regulator.
ISSN:0193-1857
1522-1547
DOI:10.1152/ajpgi.00291.2001