Source:http://linkedlifedata.com/resource/pubmed/id/10882428
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2000-9-29
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pubmed:databankReference | |
pubmed:abstractText |
Cl- apically enters the epithelium of rabbit gallbladder by a Na+-Cl- symport, sensitive to hydrochlorothiazide (HCTZ). Since HCTZ also activates an apical SITS-sensitive Cl- conductance (G(Cl)), the symport inhibition might be merely due to a short circuit of the symport by G(Cl) rather than to a direct action of HCTZ on the symporter. To examine whether the symport is directly inhibited by HCTZ and whether the symporter belongs to the family of thiazide-sensitive cotransporters (TSC), radiochemical measurements of the apical Cl- uptake, electrophysiological determinations of intracellular Cl- and Na+ activities (a(i,Cl) and a(i,Na)) with selective theta microelectrodes and molecular biology methods were used. The 13Cl- uptake proved to be a measurement of the apical unidirectional Cl- influx (Jmc) and of the symport only (without backflux components), with measuring times of 45 sec under all experiment conditions; its inhibition by HCTZ was unaffected by G(Cl) activation or abolition. After HCTZ treatment the decrease in a(i,Cl) (measured as the initial rate or in 3 min) was larger than the decrease in a(i,Na). The difference was reduced to one third in a group of epithelia in which the elicited G(Cl) was reduced to one third; moreover it was abolished in any case when G(Cl) was abolished with 10(-4) M SITS. The SITS-insensitive rate of a(i,Cl) decrease was equal to that of the a(i,Na) decrease in any case. Thus the a(i,Cl) decrease displays a component dependent on G(Cl) activation and a second component dependent on symport inhibition. Using the RT-PCR technique a cDNA fragment was obtained that was 99% identical to the corresponding region of the rabbit renal TSC isoform. The results indicate that in rabbit gallbladder epithelium HCTZ displays a dual action, namely G(Cl) activation and Na+-Cl- symport inhibition. This Na+-Cl- symporter is the first TSC found to be functionally expressed in a nonrenal or nonrenal-like epithelium.
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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/Benzothiadiazines,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Chlorides,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/Diuretics,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Drug,
http://linkedlifedata.com/resource/pubmed/chemical/SLC12A3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium Chloride Symporter Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium Chloride Symporters,
http://linkedlifedata.com/resource/pubmed/chemical/Symporters,
http://linkedlifedata.com/resource/pubmed/chemical/thiazide receptor
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0022-2631
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
176
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
53-65
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pubmed:dateRevised |
2005-11-17
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pubmed:meshHeading |
pubmed-meshheading:10882428-Amino Acid Sequence,
pubmed-meshheading:10882428-Animals,
pubmed-meshheading:10882428-Base Sequence,
pubmed-meshheading:10882428-Benzothiadiazines,
pubmed-meshheading:10882428-Carrier Proteins,
pubmed-meshheading:10882428-Cells, Cultured,
pubmed-meshheading:10882428-Chlorides,
pubmed-meshheading:10882428-DNA, Complementary,
pubmed-meshheading:10882428-Diuretics,
pubmed-meshheading:10882428-Epithelial Cells,
pubmed-meshheading:10882428-Gallbladder,
pubmed-meshheading:10882428-Humans,
pubmed-meshheading:10882428-Intracellular Fluid,
pubmed-meshheading:10882428-Male,
pubmed-meshheading:10882428-Molecular Sequence Data,
pubmed-meshheading:10882428-Rabbits,
pubmed-meshheading:10882428-Receptors, Drug,
pubmed-meshheading:10882428-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:10882428-Sequence Homology, Amino Acid,
pubmed-meshheading:10882428-Sodium,
pubmed-meshheading:10882428-Sodium Chloride Symporter Inhibitors,
pubmed-meshheading:10882428-Sodium Chloride Symporters,
pubmed-meshheading:10882428-Symporters
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pubmed:year |
2000
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pubmed:articleTitle |
Apical Na+-Cl- symport in rabbit gallbladder epithelium: a thiazide-sensitive cotransporter (TSC).
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pubmed:affiliation |
Dipartimento di Fisiologia e Biochimica Generali, Sezione di Fisiologia Generale, Università degli Studi di Milano, Via Celoria 26, I-20133 Milan, Italy.
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pubmed:publicationType |
Journal Article
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