Abstract
Barakol is a purified extract of Cassia siamea, a plant that has been used as a laxative in traditional medicine. In this study, the effect of barakol on anion transport across the rat colon epithelium was investigated. Colonic epithelium was mounted in Ussing chambers and bathed with Ringer's solution. Addition of 1 mM barakol to the basolateral solution produced a slow increase in short-circuit current (Isc) in proximal colon and distal colon by 24.5 ± 2.2 and 24.2 ± 1.4 μA/cm2, respectively. Barakol increased Isc in a concentration-dependent manner with an EC50 value of 0.4 mM. The barakol-stimulated increase in Isc was inhibited by subsequent treatment with 500 μM diphenylamine-2-carboxylic acid or 400 μM glibenclamide added to the apical solution and 200 μM bumetanide added to the basolateral solution. Pretreatment of the tissues with 200 μM bumetanide, but not 10 μM amiloride, completely abolished the barakol-increased Isc. Ion substitution experiments showed an inhibition of barakol-stimulated Isc in chloride-free solution but not in bicarbonate-free solution. In addition, pretreatment of tissues with 10 μM tetrodotoxin or 10 μM indomethacin, but not 1 μM atropine or 10 μM hexamethonium, partially inhibited the Isc response by barakol. The present results demonstrated the stimulatory effect of barakol on the bumetanide-sensitive chloride secretion in rat colon. The effect of barakol was partly mediated by the stimulation of submucosal nerves and through the release of cyclooxygenase metabolites. These findings thus provide an explanation for the underlying mechanism of barakol as a secretagogue in mammalian colon.
Footnotes
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This work was fully supported by The Thailand Research Fund (MRG4680196) awarded to C.D.
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This work was presented as a poster in the 14th World Congress of Pharmacology Meeting; 2002 July 7–12, San Francisco, CA [Deachapunya C, Thongsaard W, and Poonyachoti S (2002) Barakol stimulates chloride secretion in rat colon. The Pharmacologist44:A35].
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.105.084210.
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ABBREVIATIONS: DPC, diphenylamine-2-carboxylic acid; DIDS, 4,4-diisothiocyanatostilbene-2,2-disulfonic acid; PD, potential difference; Isc, short-circuit current; G, tissue conductance; TTX, tetrodotoxin; CFTR, cystic fibrosis transmembrane conductance regulator.
- Received February 1, 2005.
- Accepted April 28, 2005.
- The American Society for Pharmacology and Experimental Therapeutics
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