Linked Life Data

9512509

Source:http://linkedlifedata.com/resource/pubmed/id/9512509

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1998-7-8
pubmed:abstractText
The canalicular membrane of rat hepatocytes contains an ATP-dependent multispecific organic anion transporter, also named multidrug resistance protein 2, that is responsible for the biliary secretion of several amphiphilic organic anions. This transport function is markedly diminished in mutant rats that lack the transport protein. To assess the role of vesicle traffic in the regulation of canalicular organic anion transport, we have examined the redistribution of the transporter to the canalicular membrane and the effect of cAMP on this process in isolated hepatocyte couplets, which retain secretory polarity. The partial disruption of cell-cell contact, due to the isolation procedure, leaves the couplet with both remnant apical membranes, as a source of apical proteins, and an intact apical domain and lumen, to which these proteins are targeted. The changes in distribution of the transporter were correlated to the apical excretion of a fluorescent substrate, glutathione-methylfluorescein. The data obtained in this study show that the transport protein, endocytosed from apical membrane remnants, first is redistributed along the basolateral plasma membrane. Then it is transcytosed to the remaining apical pole in a microtubule-dependent fashion, followed by the fusion of transporter-containing vesicles with the apical membrane. The cAMP analog dibutyrylcAMP stimulates all three steps, resulting in increased apically located transport protein, glutathione-methylfluorescein transport activity and apical membrane circumference. These findings indicate that the organic anion transport capacity of the apical membrane in hepatocyte couplets is regulated by cAMP-stimulated sorting of the multidrug resistance protein 2 to the apical membrane. The relevance of this phenomenon for the intact liver is discussed.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9533
pubmed:author
pubmed:issnType
Print
pubmed:volume
111 ( Pt 8)
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1137-45
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:9512509-1-Methyl-3-isobutylxanthine, pubmed-meshheading:9512509-Animals, pubmed-meshheading:9512509-Anion Transport Proteins, pubmed-meshheading:9512509-Antineoplastic Agents, pubmed-meshheading:9512509-Biological Transport, pubmed-meshheading:9512509-Bucladesine, pubmed-meshheading:9512509-Carrier Proteins, pubmed-meshheading:9512509-Cell Membrane, pubmed-meshheading:9512509-Cyclic AMP, pubmed-meshheading:9512509-Fluoresceins, pubmed-meshheading:9512509-Glutathione, pubmed-meshheading:9512509-Intracellular Membranes, pubmed-meshheading:9512509-Liver, pubmed-meshheading:9512509-Male, pubmed-meshheading:9512509-Nocodazole, pubmed-meshheading:9512509-Phosphodiesterase Inhibitors, pubmed-meshheading:9512509-Rats, pubmed-meshheading:9512509-Rats, Mutant Strains, pubmed-meshheading:9512509-Rats, Sprague-Dawley
pubmed:year
1998
pubmed:articleTitle
Cyclic AMP stimulates sorting of the canalicular organic anion transporter (Mrp2/cMoat) to the apical domain in hepatocyte couplets.
pubmed:affiliation
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't