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 muM) 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 muM) 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 muM) and glibenclamide (500 muM) and basolateral application of chromanol 293B (30 muM), a blocker of K(v)LQT1 channels and Ba2+ ions (5 mM). Treatment of the colonic mucosa with baicalein elicited a threefold increase in cAMP production. Pretreating the colonic mucosa with carbachol (100 muM, serosal) but not thapsigargin (1 muM, 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.