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rdf:type |
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lifeskim:mentions |
umls-concept:C0007634,
umls-concept:C0013030,
umls-concept:C0021467,
umls-concept:C0021469,
umls-concept:C0021853,
umls-concept:C0034693,
umls-concept:C0034721,
umls-concept:C0221908,
umls-concept:C0441655,
umls-concept:C0851285,
umls-concept:C0872383,
umls-concept:C1333700,
umls-concept:C1621574
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pubmed:issue |
6
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pubmed:dateCreated |
2006-12-15
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pubmed:abstractText |
The present study investigated the effect of dopamine D1-like receptor stimulation on the Cl-/HCO3- exchange activity in rat intestinal epithelial IEC-6 cells. The Cl-/HCO3- exchange activity was found to be a chloride-dependent, DIDS-sensitive and niflumate-insensitive process. The presence of the SLC26A6 anion exchanger was detected by both RT-PCR and immunoblotting analysis in IEC-6 cells, in which three different small interfering RNAs (siRNAs) targeting SLC26A6 markedly inhibited Cl-/HCO3- exchange. Activation of dopamine D1-like receptors with SKF 38393 inhibited Cl-/HCO3- exchanger activity, this being antagonized by the D1 selective antagonist SKF 83566. However, effects of SKF 38393 were maximal at 5 min of exposure to the agonist and rapidly diminished with no effect at 15 min, suggestive of agonist-induced desensitization of D1-like receptors. Pretreatment of cells with heparin, a non-selective inhibitor of G protein-coupled receptor kinases (GRKs), prevented the observed attenuation of SKF 38393-induced inhibition of Cl-/HCO3- exchange. Overnight pretreatment with anti-GRK6A and anti-GRK6B, but not with anti-GRK4 antibodies, prevented the loss of SKF 38393-mediated effects. Both PKA and PKC signaling pathways participate in SKF 38393-mediated inhibition of Cl-/HCO3- exchange. These findings suggest that SLC26A6 is at least one of the anion exchanger's family members responsible for Cl-/HCO3- exchange in IEC-6 cells. Dopamine D1 receptors in IEC-6 rapidly desensitize to D1-like agonist stimulation and GRK 6, but not GRK 4, appear to be involved in agonist-mediated responsiveness and desensitization.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2,3,4,5-Tetrahydro-7,8-dihydroxy-1-p...,
http://linkedlifedata.com/resource/pubmed/chemical/Chloride-Bicarbonate Antiporters,
http://linkedlifedata.com/resource/pubmed/chemical/Dopamine Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Dopamine Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/G-Protein-Coupled Receptor Kinase 4,
http://linkedlifedata.com/resource/pubmed/chemical/G-Protein-Coupled Receptor Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/G-protein-coupled receptor kinase 6,
http://linkedlifedata.com/resource/pubmed/chemical/Gprk2l protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Heparin,
http://linkedlifedata.com/resource/pubmed/chemical/Heparin Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Dopamine D1,
http://linkedlifedata.com/resource/pubmed/chemical/SK&F 83566
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pubmed:status |
MEDLINE
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pubmed:issn |
1015-8987
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pubmed:author |
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pubmed:copyrightInfo |
Copyright 2006 S. Karger AG, Basel.
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pubmed:issnType |
Print
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pubmed:volume |
18
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
347-60
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:17170521-2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine,
pubmed-meshheading:17170521-Animals,
pubmed-meshheading:17170521-Cells, Cultured,
pubmed-meshheading:17170521-Chloride-Bicarbonate Antiporters,
pubmed-meshheading:17170521-Dopamine Agonists,
pubmed-meshheading:17170521-Dopamine Antagonists,
pubmed-meshheading:17170521-G-Protein-Coupled Receptor Kinase 4,
pubmed-meshheading:17170521-G-Protein-Coupled Receptor Kinases,
pubmed-meshheading:17170521-Gene Expression,
pubmed-meshheading:17170521-Heparin,
pubmed-meshheading:17170521-Heparin Antagonists,
pubmed-meshheading:17170521-Immunohistochemistry,
pubmed-meshheading:17170521-Intestinal Mucosa,
pubmed-meshheading:17170521-Intestines,
pubmed-meshheading:17170521-Protein-Serine-Threonine Kinases,
pubmed-meshheading:17170521-RNA, Messenger,
pubmed-meshheading:17170521-Rats,
pubmed-meshheading:17170521-Receptors, Dopamine D1
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pubmed:year |
2006
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pubmed:articleTitle |
Dopamine D1-like receptor-mediated inhibition of Cl/HCO3- exchanger activity in rat intestinal epithelial IEC-6 cells is regulated by G protein-coupled receptor kinase 6 (GRK 6).
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pubmed:affiliation |
Institute of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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