Cellular mechanism for potentiation of Ca2+-mediated Cl- secretion by the flavonoid baicalein in intestinal epithelia.
Flavonoids belong to a large group of plant polyphenols that are consumed daily in large amounts. Our previous findings have shown that baicalein, a major flavonoid derived from the medicinal herb Scutellariae radix, induces Cl(-) secretion across rat colonic mucosa. The current study examines the effect of baicalein on Cl(-) secretion in human colonic epithelial (T84) cells and its interaction with Ca(2+)- and cAMP-dependent secretagogues. We have employed a technique that allows concurrent monitoring of short-circuit current (I(SC)) and [Ca(2+)](i) in polarized epithelium. Basolateral application of baicalein induced a concentration-dependent increase in I(SC). The increase in I(SC) was because of Cl(-) secretion and was not accompanied by any discernible increase in [Ca(2+)](i). Baicalein acted synergistically with Ca(2+)- but not cAMP-dependent secretagogues. In the presence of baicalein, the carbachol and histamine induced increases in I(SC) that were markedly potentiated while increases in [Ca(2+)](i) were not significantly enhanced. Baicalein treatment uncoupled Cl(-) secretion from inhibitory effects normally generated by muscarinic activation. Baicalein treatment also resulted in increased cAMP content and activated PKA activity. Nystatin permeabilization studies revealed that baicalein stimulated an apical Cl(-) current but did not activate any basolateral K(+) current. These data suggest that baicalein potentiates Ca(2+)-mediated Cl(-) secretion through a signaling pathway involving cAMP and protein kinase A, most likely through the cystic fibrosis transmembrane conductance regulator in the apical membrane.
Yue
Grace Gar-Lee
GG
Department of Physiology, The Chinese University of Hong Kong, Shatin, N.T. Hong Kong, China.
Yip
Tiffany Wai-Nga
TW
Huang
Yu
Y
Ko
Wing-Hung
WH
D000975:Antioxidants / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002460:Cell Line; D002712:Chlorides / Q000378:metabolism*; D018679:Cholinergic Agonists / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004357:Drug Synergism; D044950:Flavanones; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D007476:Ionophores / Q000494:pharmacology; D009761:Nystatin / Q000494:pharmacology
D000975:Antioxidants; D002712:Chlorides; D018679:Cholinergic Agonists; D044950:Flavanones; D005419:Flavonoids; D007476:Ionophores; D009761:Nystatin; D005576:Colforsin; C006680:baicalein; D002217:Carbachol; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D002118:Calcium