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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1 Pt 1
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pubmed:dateCreated |
1992-2-21
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pubmed:abstractText |
Ca(2+)-dependent secretagogues (e.g., carbachol, histamine, ionomycin, and 4-bromo-A23187) have relatively transient effects on chloride secretion, even if there is a sustained increase in cytosolic calcium ([Ca2+]i) (as for the ionophores). Because these agents increase both [Ca2+]i and protein kinase C (PKC) activity, chloride secretion might be stimulated by [Ca2+]i and terminated by PKC activity. We tested the effect of a PKC activator, phorbol 12-myristate 13-acetate (PMA), on Cl- secretion by T84 cell monolayers by measuring short-circuit current (Isc). PMA alone had no effect on Isc but potentiated increases in Isc when added 10 min or less before Ca(2+)-dependent secretagogues. Chelation of [Ca2+]i with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid inhibited the increases both in [Ca2+]i and Isc induced by carbachol with or without brief PMA pretreatment. Longer preincubations with PMA inhibited Isc responses to Ca(2+)-dependent secretagogues, even when increased [Ca2+]i was sustained by ionophores. Inhibitors of PKC could reverse the inhibitory effect of PMA but did not reverse the potentiating effect. The effects of PMA on Cl- secretion were reproduced by 1,2-dioctanoyl-sn-glycerol and were mirrored by effects on K+ channel opening. Thus PMA has dual effects on chloride secretion. Initially, it exerts a stimulatory action and subsequently an inhibitory action. The stimulatory effect only occurs if Ca(2+)-dependent secretion is ongoing. The inhibitory effect of PMA is mediated by PKC and cannot be overcome by increasing [Ca2+]i.
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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/1-(5-Isoquinolinesulfonyl)-2-Methylp...,
http://linkedlifedata.com/resource/pubmed/chemical/Alkaloids,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Chlorides,
http://linkedlifedata.com/resource/pubmed/chemical/Isoquinolines,
http://linkedlifedata.com/resource/pubmed/chemical/Piperazines,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Rubidium,
http://linkedlifedata.com/resource/pubmed/chemical/Sphingosine,
http://linkedlifedata.com/resource/pubmed/chemical/Staurosporine,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0002-9513
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
262
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
C15-22
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:1733229-1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine,
pubmed-meshheading:1733229-Alkaloids,
pubmed-meshheading:1733229-Calcium,
pubmed-meshheading:1733229-Cell Line,
pubmed-meshheading:1733229-Chlorides,
pubmed-meshheading:1733229-Colon,
pubmed-meshheading:1733229-Humans,
pubmed-meshheading:1733229-Intestinal Mucosa,
pubmed-meshheading:1733229-Isoquinolines,
pubmed-meshheading:1733229-Osmolar Concentration,
pubmed-meshheading:1733229-Piperazines,
pubmed-meshheading:1733229-Protein Kinase Inhibitors,
pubmed-meshheading:1733229-Rubidium,
pubmed-meshheading:1733229-Sphingosine,
pubmed-meshheading:1733229-Staurosporine,
pubmed-meshheading:1733229-Tetradecanoylphorbol Acetate,
pubmed-meshheading:1733229-Time Factors
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pubmed:year |
1992
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pubmed:articleTitle |
Dual effects of a phorbol ester on calcium-dependent chloride secretion by T84 epithelial cells.
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pubmed:affiliation |
Department of Medicine, University of California, San Diego 92103.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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