Stimulation of chloride secretion by baicalein in isolated rat distal colon

Abstract

The effect of baicalein on mucosal ion transport in the rat distal colon was investigated in Ussing chambers. Mucosal addition of baicalein (1–100 μM) 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 μM) 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 μM) and glibenclamide (500 μM) and basolateral application of chromanol 293B (30 μM), a blocker of KvLQT1 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 μM, serosal) but not thapsigargin (1 μM, 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.

Rutaecarpine Induces Chloride Secretion across Rat Isolated Distal Colon

“…It is noteworthy that Rut-induced I SC response is restored by the increase in intracellular cAMP level with an adenylate cyclase stimulator forskolin in the presence of indomethacin. The similar result was reported in rat colonic mucosa treated with baicalein (Ko et al, 2002). Determination of PGE 2 with enzyme-linked immunosorbent assay showed that a large part of Rut-mediated stimulation of Cl Ϫ secretion was occurred through prostaglandins release and synthesis mostly via activation of E-prostanoid receptors.…”

Barakol Extracted from Cassia siamea Stimulates Chloride Secretion in Rat Colon

“…In addition, pretreatment with the loop diuretic bumetanide completely inhibited the barakol-stimulated Isc. All of these findings were consistent with stimulation of transepithelial Cl Ϫ secretion in human and rat colon (Dharmsathaphorn et al, 1985;Ko et al, 2002;Kunzelman and Mall, 2002). The finding that the increase in Isc by barakol was not affected by the presence of the Na ϩ channel blocker amiloride indicates that barakol did not stimulate electrogenic Na ϩ absorption.…”

“…Our finding was consistent with Cl Ϫ secretion induced by other plant-derived bioactive compounds, especially flavonoid baicalein. Baicalein has been shown to stimulate Cl Ϫ secretion across rat colonic epithelium by the activation of the cAMP-dependent apical Cl Ϫ channel and the basolateral K ϩ channels (Ko et al, 2002). From studies in human colonic cancer cells (T84 cells), baicalein was found to potentiate the Ca 2ϩ -mediated Cl Ϫ secretion via an accumulation of cAMP and activation of protein kinase A activity (Yue et al, 2004).…”

The Chemopreventive Agent Resveratrol Stimulates Cyclic AMP–Dependent Chloride SecretionIn vitro

“…Other known flavonoids, e.g., flavopiridol, genistein and apigenin, are either direct chloride secretagogues at high doses or potentiate responses to other stimuli at low doses in Calu-3 cells (26), T 84 colonic epithelial cells (27 -30) and in rat distal colon (31,32).…”