scholarly journals Opioids and efflux transporters. Part 1: P-Glycoprotein substrate activity of N-substituted analogs of meperidine

2007 ◽  
Vol 17 (5) ◽  
pp. 1160-1162 ◽  
Author(s):  
Susan L. Mercer ◽  
Hazem E. Hassan ◽  
Christopher W. Cunningham ◽  
Natalie D. Eddington ◽  
Andrew Coop
Keyword(s):  
Efflux Transporters ◽  
P Glycoprotein

scholarly journals THE MODULATION OF DRUG EFFLUX TRANSPORTER BY CURCUMIN IN MCF7 BREAST CANCER CELLS AFTER REPEATED EXPOSURE OF ENDOXIFEN AND ESTRADIOL

2018 ◽  
Vol 10 (1) ◽  
pp. 102
Author(s):  
Robby Hertanto ◽  
Wilson Bastian ◽  
Paramita . ◽  
Melva Louisa
Keyword(s):  
Breast Cancer ◽  
Cell Viability ◽  
Mrna Expression ◽  
Rna Extraction ◽  
Efflux Transporters ◽  
Drug Efflux ◽  
Mcf7 Cells ◽  
Total Rna ◽  
P Glycoprotein ◽  
Drug Efflux Transporters

Objective: The aim of the present study was to determine whether curcumin (CM) can prevent drug sensitivity of breast cancer (BC) cells when E andβ-E2 are administered together and whether the underlying mechanism involves modulation of drug efflux transporters.Methods: MCF7 BC cells were treated with the vehicle only, E+β-E2, or E+β-E2+CM repeatedly for 8 weeks. Afterward, the cells were harvested,counted, and isolated for total RNA extraction. Total RNA was then processed into cDNA and further processed for the determination of mRNAexpression patterns of drug efflux transporters (P-glycoprotein, BCRP, and MRP1).Results: Decreased sensitivity of BC cells was shown by the increased cell viability of MCF7 cells after 8 weeks. This condition was accompanied withincreased mRNA expression of P-glycoprotein, BCRP, and MRP1 in cells treated with E+β-E2, as compared with the vehicle only. CM, administered incombination with E+β-E2, resulted in decreased cell viability versus E and β-E2 and also decreased in mRNA expression of P-glycoprotein, BCRP, andMRP1.Conclusion: CM partially reversed the sensitivity loss of BC cells to E in the presence of β-E2 by modulating drug efflux transporters.

scholarly journals Expression and Function of Organic Anion Transporting Polypeptides in the Human Brain: Physiological and Pharmacological Implications

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 834
Author(s):  
Anima M. Schäfer ◽  
Henriette E. Meyer zu Schwabedissen ◽  
Markus Grube
Keyword(s):  
Organic Anion ◽  
Physiological Role ◽  
Point Of View ◽  
Efflux Transporters ◽  
Organic Anion Transporting Polypeptides ◽  
Current State ◽  
P Glycoprotein ◽  
The Central Nervous System ◽  
And Function ◽  
Uptake Transporters

The central nervous system (CNS) is an important pharmacological target, but it is very effectively protected by the blood–brain barrier (BBB), thereby impairing the efficacy of many potential active compounds as they are unable to cross this barrier. Among others, membranous efflux transporters like P-Glycoprotein are involved in the integrity of this barrier. In addition to these, however, uptake transporters have also been found to selectively uptake certain compounds into the CNS. These transporters are localized in the BBB as well as in neurons or in the choroid plexus. Among them, from a pharmacological point of view, representatives of the organic anion transporting polypeptides (OATPs) are of particular interest, as they mediate the cellular entry of a variety of different pharmaceutical compounds. Thus, OATPs in the BBB potentially offer the possibility of CNS targeting approaches. For these purposes, a profound understanding of the expression and localization of these transporters is crucial. This review therefore summarizes the current state of knowledge of the expression and localization of OATPs in the CNS, gives an overview of their possible physiological role, and outlines their possible pharmacological relevance using selected examples.

scholarly journals Extract from Dioscorea bulbifera L. rhizomes aggravate pirarubicin-induced cardiotoxicity by inhibiting the expression of P-glycoprotein and multidrug resistance-associated protein 2 in the mouse liver

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Li-rui Sun ◽  
Qiu-shi Guo ◽  
Wei Zhou ◽  
Min Li
Keyword(s):  
Multidrug Resistance ◽  
Mouse Liver ◽  
Adverse Reactions ◽  
Heart Tissue ◽  
Efflux Transporters ◽  
Glycoprotein P ◽  
Chinese Herbal ◽  
Good Safety Profile ◽  
P Glycoprotein ◽  
Dioscorea Bulbifera

AbstractChinese herbal medicine is widely used because it has a good safety profile and few side effects. However, the risk of adverse drug reactions caused by herb-drug interactions (HDIs) is often overlooked. Therefore, the task of identifying possible HDIs and elucidating their mechanisms is of great significance for the prevention and treatment of HDI-related adverse reactions. Since extract from Dioscorea bulbifera L. rhizomes (DB) can cause various degrees of liver damage, it is speculated that HDIs may occur between DB extract and chemicals metabolized or excreted by the liver. Our study revealed that the cardiotoxicity of pirarubicin (THP) was increased by co-administration of DB, and the expression of P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (Mrp2) in the liver was inhibited by DB extract, which led to the accumulation of THP in heart tissue. In conclusion, there are risks of the co-administration of DB extract and THP. The mechanism of HDIs can be better revealed by targeting the efflux transporters.

scholarly journals Malaria in pregnancy regulates P‐glycoprotein (P‐gp/ Abcb1a ) and ABCA1 efflux transporters in the Mouse Visceral Yolk Sac

2020 ◽  
Vol 24 (18) ◽  
pp. 10636-10647 ◽  
Author(s):  
Lilian M. Martinelli ◽  
Klaus N. Fontes ◽  
Mila W. Reginatto ◽  
Cherley B. V. Andrade ◽  
Victoria R. S. Monteiro ◽  
...  
Keyword(s):  
Yolk Sac ◽  
Malaria In Pregnancy ◽  
Efflux Transporters ◽  
Glycoprotein P ◽  
P Glycoprotein ◽  
Visceral Yolk Sac ◽  
In Pregnancy

Commonly used nonionic surfactants interact differently with the human efflux transporters ABCB1 (p-glycoprotein) and ABCC2 (MRP2)

2010 ◽  
Vol 76 (2) ◽  
pp. 260-268 ◽  
Author(s):  
Ulrike Hanke ◽  
Karen May ◽  
Veronika Rozehnal ◽  
Stefan Nagel ◽  
Werner Siegmund ◽  
...  
Keyword(s):  
Nonionic Surfactants ◽  
Efflux Transporters ◽  
P Glycoprotein

scholarly journals Malaria in pregnancy regulates P-glycoprotein (P-gp/Abcb1a) and ABCA1 efflux transporters in the mouse visceral yolk sac

2020 ◽  
Author(s):  
Lilian M. Martinelli ◽  
Klaus N. Fontes ◽  
Mila W. Reginatto ◽  
Cherley B. V. Andrade ◽  
Victoria R. S. Monteiro ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Yolk Sac ◽  
Malaria In Pregnancy ◽  
Efflux Transporters ◽  
Fetal Membrane ◽  
Toxic Substances ◽  
Cancer Resistance ◽  
P Glycoprotein ◽  
And Function ◽  
In Pregnancy

AbstractMalaria in pregnancy (MiP) induces intrauterine growth restriction (IUGR) and preterm labor (PTL). However, its effects on yolk sac morphology and function are largely unexplored. We hypothesized that MiP modifies yolk sac morphology and efflux transport potential by modulating ABC efflux transporters. C57BL/6 mice injected with Plasmodium berghei ANKA (5×105 infected-erythrocytes) at gestational day (GD) 13.5, were subjected to yolk sac membrane harvesting at GD18.5 for histology, qPCR and immunohistochemistry. MiP did not alter the volumetric proportion of the yolk sac’s histological components. However, it increased levels of Abcb1a mRNA (encoding P-glycoprotein) and macrophage migration inhibitory factor (Mif-chemokine), whilst decreasing Abcg1 (P<0.05); without altering Abca1, Abcb1b, Abcg2, Snat1, Snat2, interleukin (Il)-1 β and C-C Motif Chemokine Ligand 2 (Ccl2). Transcripts of Il-6, chemokine (C-X-C motif) ligand 1 (Cxcl1), Glut1 and Snat4 were not detectible. ABCA1, ABCG1, breast cancer resistance protein (BCRP) and P-gp, were primarily immunolocalized to the cell membranes and cytoplasm of endodermic epithelium but also in the mesothelium and in the endothelium of mesodermic blood vessels. Intensity of P-gp labeling was stronger in both endodermic epithelium and mesothelium, whereas ABCA1 labeling increased in the endothelium of the mesodermic blood vessels. The presence of ABC transporters in the yolk sac wall suggest that this fetal membrane acts as an important protective gestational barrier. Changes in ABCA1 and P-gp in MiP may alter the biodistribution of toxic substances, xenobiotics, nutrients and immunological factors within the fetal compartment and participate in the pathogenesis of malaria induced-IUGR and PTL.

scholarly journals Substrate recognition by P-glycoprotein efflux transporters: Structure-ATPase activity relationship of diverse chemicals and agrochemicals

2013 ◽  
Vol 38 (3) ◽  
pp. 112-122 ◽  
Author(s):  
Satoshi Kanaoka ◽  
Yasuhisa Kimura ◽  
Masaaki Fujikawa ◽  
Yoshiaki Nakagawa ◽  
Kazumitsu Ueda ◽  
...  
Keyword(s):  
Atpase Activity ◽  
Substrate Recognition ◽  
Activity Relationship ◽  
Efflux Transporters ◽  
P Glycoprotein ◽  
Relationship Of

scholarly journals Role of P-Glycoprotein in the Distribution of the HIV Protease Inhibitor Atazanavir in the Brain and Male Genital Tract

2013 ◽  
Vol 58 (3) ◽  
pp. 1713-1722 ◽  
Author(s):  
Kevin R. Robillard ◽  
Gary N. Y. Chan ◽  
Guijin Zhang ◽  
Charles la Porte ◽  
William Cameron ◽  
...  
Keyword(s):  
Protease Inhibitor ◽  
Genital Tract ◽  
Seminal Fluid ◽  
Hiv Protease ◽  
Efflux Transporters ◽  
Drug Efflux ◽  
Male Genital Tract ◽  
Hiv Protease Inhibitor ◽  
P Glycoprotein ◽  
Male Genital

ABSTRACTThe blood-testis barrier and blood-brain barrier are responsible for protecting the male genital tract and central nervous system from xenobiotic exposure. In HIV-infected patients, low concentrations of antiretroviral drugs in cerebrospinal fluid and seminal fluid have been reported. One mechanism that may contribute to reduced concentrations is the expression of ATP-binding cassette drug efflux transporters, such as P-glycoprotein (P-gp). The objective of this study was to investigatein vivothe tissue distribution of the HIV protease inhibitor atazanavir in wild-type (WT) mice, P-gp/breast cancer resistance protein (Bcrp)-knockout (Mdr1a−/−,Mdr1b−/−, andAbcg2−/−triple-knockout [TKO]) mice, and Cyp3a−/−(Cyp) mice. WT mice and Cyp mice were pretreated with a P-gp/Bcrp inhibitor, elacridar (5 mg/kg of body weight), and the HIV protease inhibitor and boosting agent ritonavir (2 mg/kg intravenously [i.v.]), respectively. Atazanavir (10 mg/kg) was administered i.v. Atazanavir concentrations in plasma (Cplasma), brain (Cbrain), and testes (Ctestes) were quantified at various times by liquid chromatography-tandem mass spectrometry. In TKO mice, we demonstrated a significant increase in atazanavirCbrain/Cplasma(5.4-fold) andCtestes/Cplasma(4.6-fold) ratios compared to those in WT mice (P< 0.05). Elacridar-treated WT mice showed a significant increase in atazanavirCbrain/Cplasma(12.3-fold) andCtestes/Cplasma(13.5-fold) ratios compared to those in vehicle-treated WT mice. In Cyp mice pretreated with ritonavir, significant (P< 0.05) increases in atazanavirCbrain/Cplasma(1.8-fold) andCtestes/Cplasma(9.5-fold) ratios compared to those in vehicle-treated WT mice were observed. These data suggest that drug efflux transporters, i.e., P-gp, are involved in limiting the ability of atazanavir to permeate the rodent brain and genital tract. Since these transporters are known to be expressed in humans, they could contribute to the low cerebrospinal and seminal fluid antiretroviral concentrations reported in the clinic.

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