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 M) elicited a concentrationdependent short-circuit current (Isc) response. The increase in Isc was mainly due to Cl Ϫ secretion. The presence of mucosal indomethacin (10 M) significantly reduced both the basal and subsequent baicalein-evoked Isc responses. The

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... uced Isc were inhibited by mucosal application of diphenylamine-2-carboxylic acid (100 M) and glibenclamide (500 M) and basolateral application of chromanol 293B (30 M), a blocker of KvLQT1 channels and Ba 2ϩ ions (5 mM). Treatment of the colonic mucosa with baicalein elicited a threefold increase in cAMP production. Pretreating the colonic mucosa with carbachol (100 M, serosal) but not thapsigargin (1 M, both sides) abolished the baicalein-induced Isc. Addition of baicalein subsequent to forskolin induced a further increase in Isc. These results indicate that the baicalein evoked Cl Ϫ secretion across rat colonic mucosa, possibly via a cAMP-dependent pathway. However, the action of baicalein cannot be solely explained by its cAMPelevating effect. Baicalein may stimulate Cl Ϫ secretion via a cAMP-independent pathway or have a direct effect on cystic fibrosis transmembrane conductance regulator.