RGD Reference Report - Mrp2 modulates the activity of chloride channels in isolated hepatocytes. - Rat Genome Database

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Mrp2 modulates the activity of chloride channels in isolated hepatocytes.

Authors: Li, X  Weinman, SA 
Citation: Li X and Weinman SA, Hepatology. 2002 Jul;36(1):65-71.
RGD ID: 1598603
Pubmed: PMID:12085350   (View Abstract at PubMed)
DOI: DOI:10.1053/jhep.2002.33998   (Journal Full-text)

Adenosine triphosphate binding cassette family transport proteins are important organic ion transporters in hepatocytes but these molecules may also exhibit other functions. In the present study we have measured the effects of substrates of the canalicular organic ion transporter multidrug resistance associated protein 2 (Mrp2) on chloride channel activation and cell volume regulation. We found that substrates such as leukotriene D(4), 17-beta-estradiol glucuronide, and the leukotriene inhibitor MK-571 accelerated the activation of chloride channels by cell swelling and activated chloride channels in cytokine-pretreated hepatocytes. Two conjugated estrogens that are not Mrp2 substrates did not produce this effect. Hepatocytes derived from a strain of transport-deficient rats (TR(-)), which lack Mrp2 expression, showed none of these substrate effects. Coincident with their ability to activate channels, the Mrp2 substrates increased the rate of volume regulatory decrease by approximately 50% (P <.01), confirming that enhanced channel activation under this condition stimulated volume regulation. In TR-hepatocytes the Mrp2 substrate had no effect on volume regulation. In conclusion, Mrp2 plays a role in regulation of chloride channel function by reducing the lag time necessary for channel activation and consequently accelerating the process of cell volume regulation. Substrates of Mrp2 affect the ability of the protein to interact with chloride channels. These findings represent an alternative function of Mrp2 in hepatocytes.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
intracellular chloride ion homeostasis  IDA 1598603 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Abcc2  (ATP binding cassette subfamily C member 2)

Additional Information