Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.44 (P-glycoprotein)
 13,344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Delivery of drugs to the brain is impeded by the activity of efflux pumps expressed by endothelial cells of brain vasculature. The ATP binding cassette (ABC) transporters, among which ABCB1/MDR1 P-glycoprotein and ABCC1/multidrug resistance-associated protein 1 are expressed in brain endothelial cells, participate in drug efflux properties of the blood-brain barrier (BBB). Searches of the EST (expressed sequence tags) database with the conserved ABC domain, conducted to identify other ABC transporters expressed in the BBB, recovered 15 ABC transporter sequences expressed in human brain cDNA libraries. One of these sequences, identical to ABCG2, was highly expressed in cultured human cerebromicrovascular endothelial cells and human brain tissue at both mRNA and protein levels. Overexpression of human ABCG2 in immortalized rat brain endothelial cells resulted in enhanced polarized abluminal to luminal transport of various substrates tested in the in vitro BBB model. Brain vessels extracted from tissue sections of nonmalignant human brain and glioblastoma tumors by laser capture microdissection microscopy and analyzed by real-time polymerase chain reaction showed higher expression of ABCG2 relative to ABCB1/MDR1 and ABCC1/MRP1. ABCG2 was up-regulated in both glioblastoma vessels and parenchymal tissue. These studies suggest a role for brain endothelial ABCG2 transporter in modulating drug delivery to the brain and in conferring drug resistance to glioblastomas.
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PMID:The expression and functional characterization of ABCG2 in brain endothelial cells and vessels. 1295 61

We have identified and partially sequenced 8 ABC transporters from an EST dataset of Sarcoptes scabiei var. hominis, the causative agent of scabies. Analysis confirmed that most of the known ABC subfamilies are represented in the EST dataset including several members of the multidrug resistance protein subfamily (ABC-C). Although P-glycoprotein (ABC-B) sequences were not found in the EST dataset, a partial P-glycoprotein sequence was subsequently obtained using a degenerate PCR strategy and library screening. Thus a total of 9 potential S. scabiei ABC transporters representing the subfamilies A, B, C, E, F and H have been identified. Ivermectin is currently used in the treatment of hyper-infested (crusted) scabies, and has also been identified as a potentially effective acaricide for mass treatment programmes in scabies-endemic communities. The observation of clinical and in vitro ivermectin resistance in 2 crusted scabies patients who received multiple treatments has raised serious concerns regarding the sustainability of such programmes. One possible mechanism for ivermectin resistance is through ABC transporters such as P-glycoprotein. This work forms an important foundation for further studies to elucidate the potential role of ABC transporters in ivermectin resistance of S. scabiei.
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PMID:Identification of ABC transporters in Sarcoptes scabiei. 1645 64

The MRPs (multi-drug resistance associated proteins; ABCC subfamily) are members of the ATP binding cassette (ABC) superfamily of transport proteins and act as cellular efflux transporters of a wide variety of substrates, in particular glutathione, glucuronide and sulphate conjugates of diverse compounds. Together with P-gp (P-glycoprotein; MDR1; ABCB1) and BCRP (breast cancer resistance protein, ABCG2) the MRPs are highly important as cellular defense against toxicants and confer multixenobiotic resistance (MXR). In aquatic ecotoxicology MXR research has mostly focussed on P-glycoprotein while the other relevant ABC transporters are widely under-appreciated. We here present complete MRP1 (ABCC1) and partial MRP3 (ABCC3) cDNAs from rainbow trout (Oncorhynchus mykiss). We identified 4398bp of the MRP1 and 3786bp of the MRP3 open reading frames (ORF) by screening the NCBI EST database and by reverse transcription-polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE) using RNA from RTgill-W1 cells. Identities with human homologs are 56% for MRP1 and 64% for MRP3.
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PMID:Identification of multi-drug resistance associated proteins MRP1 (ABCC1) and MRP3 (ABCC3) from rainbow trout (Oncorhynchus mykiss). 1996 64