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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4 Pt 1
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pubmed:dateCreated |
1993-12-3
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pubmed:abstractText |
The effect of phorbol esters on adenosine 3',5'-cyclic monophosphate (cAMP)-regulated epithelial Cl- transport was studied in T84 cells, a human colonic cell line that serves as a model for electrogenic Cl- secretion. Preincubation of T84 cell monolayers with phorbol 12-myristate 13-acetate (PMA) caused a time- and dose-dependent inhibition of the net transepithelial secretory response to 10 microM forskolin (half-maximal inhibition at a concentration of approximately 10 nM PMA and a time of 45 min). Similar inhibition was observed with phorbol 12,13-dibutyrate but not the inactive phorbol ester phorbol 12,13-diacetate. Na(+)-K(+)-2Cl- cotransporter activity, assessed by bumetanide-sensitive 86Rb+ uptake, and K+ conductance, assessed by 86Rb+ efflux, were both found to be markedly reduced by PMA with a time course that paralleled the loss of the cAMP-regulated Cl- secretory response. One- and four-hour treatment of T84 cells with 100 nM PMA caused a sustained increase in the membrane-bound fraction of protein kinase C (PKC) but a decrease in total cellular PKC. Although, at these time points, the Na(+)-K(+)-2Cl- cotransporter and K+ efflux pathways were markedly inhibited (associated with inhibition of the forskolin-stimulated transepithelial Cl- secretory response), the activity of the cAMP-regulated Cl- efflux pathway, assessed by 125I-labeled efflux, remained unaffected. With prolonged exposure to PMA (up to 10), the cAMP-regulated Cl- efflux pathway was also eventually inhibited, and transepithelial electrical resistance progressively declined.(ABSTRACT TRUNCATED AT 250 WORDS)
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Chlorides,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Forskolin,
http://linkedlifedata.com/resource/pubmed/chemical/Phorbol 12,13-Dibutyrate,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium-Potassium-Chloride Symporters,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium-Potassium-Exchanging ATPase,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0002-9513
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
265
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
C1109-17
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:8238301-Biological Transport,
pubmed-meshheading:8238301-Carrier Proteins,
pubmed-meshheading:8238301-Cell Line,
pubmed-meshheading:8238301-Cell Membrane,
pubmed-meshheading:8238301-Chlorides,
pubmed-meshheading:8238301-Colon,
pubmed-meshheading:8238301-Cyclic AMP,
pubmed-meshheading:8238301-Electrophysiology,
pubmed-meshheading:8238301-Forskolin,
pubmed-meshheading:8238301-Humans,
pubmed-meshheading:8238301-Phorbol 12,13-Dibutyrate,
pubmed-meshheading:8238301-Potassium,
pubmed-meshheading:8238301-Protein Kinase C,
pubmed-meshheading:8238301-Sodium-Potassium-Chloride Symporters,
pubmed-meshheading:8238301-Sodium-Potassium-Exchanging ATPase,
pubmed-meshheading:8238301-Tetradecanoylphorbol Acetate,
pubmed-meshheading:8238301-Time Factors
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pubmed:year |
1993
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pubmed:articleTitle |
Phorbol ester sequentially downregulates cAMP-regulated basolateral and apical Cl- transport pathways in T84 cells.
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pubmed:affiliation |
Department of Surgery, Beth Israel Hospital, Boston, Massachusetts.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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