Source:http://linkedlifedata.com/resource/pubmed/id/16135545
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2005-12-12
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pubmed:abstractText |
We investigated the effects of 5,6-dichloro-1-ethyl-1,3-dihydro-2H-benzimidazol-2-one(DCEBIO) on the Cl- secretory response of the mouse jejunum using the Ussing short-circuit current (Isc) technique. DCEBIO stimulated a concentration-dependent, sustained increase in Isc (EC50 41 +/- 1 microM). Pretreating tissues with 0.25 microM forskolin reduced the concentration-dependent increase in Isc by DCEBIO and increased the EC50 (53 +/- 5 microM). Bumetanide blocked (82 +/- 5%) the DCEBIO-stimulated Isc consistent with Cl- secretion. DCEBIO was a more potent stimulator of Cl- secretion than its parent molecule, 1-ethyl-2-benzimidazolinone. Glibenclamide or NPPB reduced the DCEBIO-stimulated Isc by >80% indicating the participation of CFTR in the DCEBIO-stimulated Isc response. Clotrimazole reduced DCEBIO-stimulated Isc by 67 +/- 15%, suggesting the participation of the intermediate conductance Ca2+-activated K+ channel (IKCa) in the DCEBIO-activated Isc response. In the presence of maximum forskolin (10 microM), the DCEBIO response was reduced and biphasic, reaching a peak response of the change in Isc of 43 +/- 5 microA/cm2 and then falling to a steady-state response of 17 +/- 10 microA/cm2 compared with DCEBIO control tissues (61 +/- 6 microA/cm2). The forskolin-stimulated Isc in the presence of DCEBIO was reduced compared with forskolin control tissues. Similar results were observed with DCEBIO and 8-BrcAMP where adenylate cyclase was bypassed. H89, a PKA inhibitor, reduced the DCEBIO-activated Isc, providing evidence that DCEBIO increased Cl- secretion via a cAMP/PKA-dependent manner. These data suggest that DCEBIO stimulates Cl- secretion of the mouse jejunum and that DCEBIO targets components of the Cl- secretory mechanism.
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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-ethyl-2-benzimidazolinone,
http://linkedlifedata.com/resource/pubmed/chemical/Benzimidazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channel Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Chlorides,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Cystic Fibrosis Transmembrane...,
http://linkedlifedata.com/resource/pubmed/chemical/Forskolin,
http://linkedlifedata.com/resource/pubmed/chemical/Intermediate-Conductance...
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0363-6143
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
290
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
C152-64
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:16135545-Animals,
pubmed-meshheading:16135545-Benzimidazoles,
pubmed-meshheading:16135545-Calcium Channel Agonists,
pubmed-meshheading:16135545-Chlorides,
pubmed-meshheading:16135545-Cyclic AMP,
pubmed-meshheading:16135545-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:16135545-Cystic Fibrosis Transmembrane Conductance Regulator,
pubmed-meshheading:16135545-Forskolin,
pubmed-meshheading:16135545-Intermediate-Conductance Calcium-Activated Potassium...,
pubmed-meshheading:16135545-Jejunum,
pubmed-meshheading:16135545-Male,
pubmed-meshheading:16135545-Mice
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pubmed:year |
2006
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pubmed:articleTitle |
DCEBIO stimulates Cl- secretion in the mouse jejunum.
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pubmed:affiliation |
Dept. of Physiology, School of Medical Sciences, Univ. of Otago, PO Box 913, Dunedin, New Zealand. kirk.hamilton@stonebow.otago.ac.nz
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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