Biomaterial Database

Excretion of GSSG and glutathione conjugates mediated by MRP1 and cMOAT/MRP2. 1998

H Suzuki, and Y Sugiyama

Graduate School of Pharmaceutical Sciences, The University of Tokyo, Japan.

It has been shown that both multidrug resistance-associated protein (MRP1) and canalicular multispecific organic anion transporter (cMOAT/MRP2) have the ability to extrude glutathione conjugates (GS-X pump activity)from cells. Therefore, they play an important role in the detoxification of xenobiotics. Using mrp1-knockout mice, it has recently been shown that MRP1/mrp1 has an important role in the export of leukotriene C4 (LTC4), a mediator of inflammation, and in protecting the body from a number of toxins, including several antitumor drugs. A comparison of the transport properties across the bile canalicular membrane in normal and mutant rats, whose cMOAT function is hereditarily defective, has shown that the physiologic role of cMOAT is to excrete LTC4, bilirubin glucuronides, 171-estradiol-170-D-glucuronide, and reduced folates. In the present review article, we summarize the substrate specificity and mechanism for the transport of these GS-X pumps, focusing on the pharmacologic and physiologic aspects. The transport activity mediated by cMOAT is also discussed in terms of a comparison between membrane vesicles from hepatocytes and cMOAT-transfected cells, and we also briefly examine the possible role of MRPI and cMOAT in the extrusion of reduced glutathione.

UI	MeSH Term	Description	Entries
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D002352	Carrier Proteins	Proteins that bind or transport specific substances in the blood, within the cell, or across cell membranes.	Binding Proteins,Carrier Protein,Transport Protein,Transport Proteins,Binding Protein,Protein, Carrier,Proteins, Carrier
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000970	Antineoplastic Agents	Substances that inhibit or prevent the proliferation of NEOPLASMS.	Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D001692	Biological Transport	The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.	Transport, Biological,Biologic Transport,Transport, Biologic
D018528	ATP-Binding Cassette Transporters	A family of MEMBRANE TRANSPORT PROTEINS that require ATP hydrolysis for the transport of substrates across membranes. The protein family derives its name from the ATP-binding domain found on the protein.	ABC Transporter,ABC Transporters,ATP-Binding Cassette Transporter,ATP Binding Cassette Transporter,ATP Binding Cassette Transporters,Cassette Transporter, ATP-Binding,Transporter, ABC,Transporter, ATP-Binding Cassette,Transporters, ABC,Transporters, ATP-Binding Cassette
D019803	Glutathione Disulfide	A GLUTATHIONE dimer formed by a disulfide bond between the cysteine sulfhydryl side chains during the course of being oxidized.	GSSG,Glutathione Disulfide, Ion(1-),Glutathione, Oxidized,Disulfide, Glutathione,Oxidized Glutathione
D026901	Membrane Transport Proteins	Membrane proteins whose primary function is to facilitate the transport of molecules across a biological membrane. Included in this broad category are proteins involved in active transport (BIOLOGICAL TRANSPORT, ACTIVE), facilitated transport and ION CHANNELS.	Biological Pump,Membrane Transport Protein,Membrane Transporter,Membrane Transporters,Metabolic Pump,Permease,Biological Pumps,Metabolic Pumps,Permeases,Pump, Biologic,Pump, Biological,Pump, Metabolic,Pumps, Biological,Pumps, Metabolic,Biologic Pump,Protein, Membrane Transport,Transport Protein, Membrane,Transport Proteins, Membrane,Transporter, Membrane,Transporters, Membrane
D027321	Anion Transport Proteins	Membrane proteins whose primary function is to facilitate the transport of negatively charged molecules (anions) across a biological membrane.	Anion Pumps,ATPHPM,Anion Pump,Anion Transport Proteins (Hepatocyte Plasma Membrane),Pump, Anion,Pumps, Anion