Berberine Reduces cAMP-Induced Chloride Secretion in T84 Human Colonic Carcinoma Cells through Inhibition of Basolateral KCNQ1 Channels.

Hdl Handle:
http://hdl.handle.net/10147/207050
Title:
Berberine Reduces cAMP-Induced Chloride Secretion in T84 Human Colonic Carcinoma Cells through Inhibition of Basolateral KCNQ1 Channels.
Authors:
Alzamora, Rodrigo; O'Mahony, Fiona; Ko, Wing-Hung; Yip, Tiffany Wai-Nga; Carter, Derek; Irnaten, Mustapha; Harvey, Brian Joseph
Affiliation:
Department of Molecular Medicine, Education and Research Centre, Royal College of, Surgeons in Ireland, Beaumont Hospital Dublin, Ireland.
Citation:
Front Physiol. 2011;2:33. Epub 2011 Jun 30.
Journal:
Frontiers in physiology
Issue Date:
1-Feb-2012
URI:
http://hdl.handle.net/10147/207050
DOI:
10.3389/fphys.2011.00033
PubMed ID:
21747769
Abstract:
Berberine is a plant alkaloid with multiple pharmacological actions, including antidiarrhoeal activity and has been shown to inhibit Cl(-) secretion in distal colon. The aims of this study were to determine the molecular signaling mechanisms of action of berberine on Cl(-) secretion and the ion transporter targets. Monolayers of T84 human colonic carcinoma cells grown in permeable supports were placed in Ussing chambers and short-circuit current measured in response to secretagogues and berberine. Whole-cell current recordings were performed in T84 cells using the patch-clamp technique. Berberine decreased forskolin-induced short-circuit current in a concentration-dependent manner (IC(50) 80 +/- 8 muM). In apically permeabilized monolayers and whole-cell current recordings, berberine inhibited a cAMP-dependent and chromanol 293B-sensitive basolateral membrane K(+) current by 88%, suggesting inhibition of KCNQ1 K(+) channels. Berberine did not affect either apical Cl(-) conductance or basolateral Na(+)-K(+)-ATPase activity. Berberine stimulated p38 MAPK, PKCalpha and PKA, but had no effect on p42/p44 MAPK and PKCdelta. However, berberine pre-treatment prevented stimulation of p42/p44 MAPK by epidermal growth factor. The inhibitory effect of berberine on Cl(-) secretion was partially blocked by HBDDE ( approximately 65%), an inhibitor of PKCalpha and to a smaller extent by inhibition of p38 MAPK with SB202190 ( approximately 15%). Berberine treatment induced an increase in association between PKCalpha and PKA with KCNQ1 and produced phosphorylation of the channel. We conclude that berberine exerts its inhibitory effect on colonic Cl(-) secretion through inhibition of basolateral KCNQ1 channels responsible for K(+) recycling via a PKCalpha-dependent pathway.
Language:
eng
ISSN:
1664-042X (Electronic); 1664-042X (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorAlzamora, Rodrigoen_GB
dc.contributor.authorO'Mahony, Fionaen_GB
dc.contributor.authorKo, Wing-Hungen_GB
dc.contributor.authorYip, Tiffany Wai-Ngaen_GB
dc.contributor.authorCarter, Dereken_GB
dc.contributor.authorIrnaten, Mustaphaen_GB
dc.contributor.authorHarvey, Brian Josephen_GB
dc.date.accessioned2012-02-01T09:58:04Z-
dc.date.available2012-02-01T09:58:04Z-
dc.date.issued2012-02-01T09:58:04Z-
dc.identifier.citationFront Physiol. 2011;2:33. Epub 2011 Jun 30.en_GB
dc.identifier.issn1664-042X (Electronic)en_GB
dc.identifier.issn1664-042X (Linking)en_GB
dc.identifier.pmid21747769en_GB
dc.identifier.doi10.3389/fphys.2011.00033en_GB
dc.identifier.urihttp://hdl.handle.net/10147/207050-
dc.description.abstractBerberine is a plant alkaloid with multiple pharmacological actions, including antidiarrhoeal activity and has been shown to inhibit Cl(-) secretion in distal colon. The aims of this study were to determine the molecular signaling mechanisms of action of berberine on Cl(-) secretion and the ion transporter targets. Monolayers of T84 human colonic carcinoma cells grown in permeable supports were placed in Ussing chambers and short-circuit current measured in response to secretagogues and berberine. Whole-cell current recordings were performed in T84 cells using the patch-clamp technique. Berberine decreased forskolin-induced short-circuit current in a concentration-dependent manner (IC(50) 80 +/- 8 muM). In apically permeabilized monolayers and whole-cell current recordings, berberine inhibited a cAMP-dependent and chromanol 293B-sensitive basolateral membrane K(+) current by 88%, suggesting inhibition of KCNQ1 K(+) channels. Berberine did not affect either apical Cl(-) conductance or basolateral Na(+)-K(+)-ATPase activity. Berberine stimulated p38 MAPK, PKCalpha and PKA, but had no effect on p42/p44 MAPK and PKCdelta. However, berberine pre-treatment prevented stimulation of p42/p44 MAPK by epidermal growth factor. The inhibitory effect of berberine on Cl(-) secretion was partially blocked by HBDDE ( approximately 65%), an inhibitor of PKCalpha and to a smaller extent by inhibition of p38 MAPK with SB202190 ( approximately 15%). Berberine treatment induced an increase in association between PKCalpha and PKA with KCNQ1 and produced phosphorylation of the channel. We conclude that berberine exerts its inhibitory effect on colonic Cl(-) secretion through inhibition of basolateral KCNQ1 channels responsible for K(+) recycling via a PKCalpha-dependent pathway.en_GB
dc.language.isoengen_GB
dc.titleBerberine Reduces cAMP-Induced Chloride Secretion in T84 Human Colonic Carcinoma Cells through Inhibition of Basolateral KCNQ1 Channels.en_GB
dc.contributor.departmentDepartment of Molecular Medicine, Education and Research Centre, Royal College of, Surgeons in Ireland, Beaumont Hospital Dublin, Ireland.en_GB
dc.identifier.journalFrontiers in physiologyen_GB
dc.description.provinceLeinster-

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