Drug‐Metabolizing Enzymes and Transporters: Expression in the Human Prostate and Roles in Prostate Drug Disposition

Obligacion, Regina; Murray, Michael T.; Ramzan, Iqbal

doi:10.2164/jandrol.05113

Cited by 24 publications

(13 citation statements)

References 116 publications

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“…In fact, fluorescent prazosin has been used to probe BCRP function and even label the BCRP efflux transporter (Zhou et al, 2009). Furthermore, BCRP efflux transporters have been shown to be expressed in high abundance in the prostate gland (Obligacion, Murray, & Ramzan, 2006). This leads to the exciting hypothesis that if the majority of the α 1A -adrenoceptors were located intracellularly, then ligands such as prazosin that are able to penetrate the membrane and enter the smooth muscle cell but have a high affinity for efflux transporters like BCRP would be less effective as they would get pumped out of the cell more quickly.…”

Section: Breast Cancer Resistance Protein Efflux Transportersmentioning

confidence: 99%

What makes the α_1A‐adrenoceptor gene product assume an α_1L‐adrenoceptor phenotype?

White

Silva

Lim

et al. 2019

British J Pharmacology

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The α1A‐adrenoceptor is abundantly expressed in the lower urinary tract and is the principal therapeutic target for the symptomatic treatment of lower urinary tract symptoms in men. Prazosin has a lower affinity for the lower urinary tract α1A‐adrenoceptor than α1A‐adrenoceptors found in other parts of the body. This has led to the lower urinary tract α1A‐adrenoceptor being subclassified as an α1L‐adrenoceptor. It was demonstrated that this pharmacologically distinct α1L‐adrenoceptor is a product of the α1A‐adrenoceptor gene, but the mechanism by which this altered phenotype is achieved remains a mystery. Hypotheses for this altered pharmacology include the presence of an interacting protein such as cysteine‐rich with EGF‐like domain (CRELD) 1 or other GPCRs such as the CXCR2 chemokine or 5‐HT1B receptor. Alternatively, the influence of breast cancer resistance protein (BCRP) efflux transporters on the pharmacology of α1A‐adrenoceptors has also been investigated. These and other hypotheses will be described and discussed in this review. Linked Articles This article is part of a themed section on Adrenoceptors—New Roles for Old Players. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.14/issuetoc

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Section: Breast Cancer Resistance Protein Efflux Transportersmentioning

confidence: 99%

What makes the α_1A‐adrenoceptor gene product assume an α_1L‐adrenoceptor phenotype?

White

Silva

Lim

et al. 2019

British J Pharmacology

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“…Many transporters have been discovered in tissues of the liver, kidney, and intestine (Obligacion et al, 2006;Klaassen and Lu, 2008;Delou et al, 2009;Klaassen and Aleksunes, 2010). Among them, efflux transporters and influx transporters are related to drug delivery (Gaudana et al, 2010;Su et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Expression of Efflux Transporters in Human Ocular Tissues

Chen

Zang

et al. 2013

Drug Metab Dispos

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To investigate the expression profiles of efflux transporters in human ocular tissues, quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemistry were used to obtain the relative mRNA and protein expressions of various efflux transporters in human ocular tissues. The cornea, conjunctiva, irisciliary body (ICB), retina and choroid, human corneal epithelial cell line (HCEC), and human retinal pigment epithelial cell line (ARPE-19) were examined for the expressions of multidrug resistanceassociated proteins 1-7 (MRP1-7), multidrug resistance 1 (MDR1) P-glycoprotein, lung resistance protein (LRP), and breast cancerresistance protein (BCRP). The expression sites and patterns of efflux transporters were significantly different in ocular tissues, HCEC, and ARPE-19, as well as the expression profiles of efflux transporters in mRNA and protein levels in ocular tissues. At the protein level, MRP1-7, MDR1, and LRP were expressed in the corneal epithelium; MRP1-7, MDR1, LRP, and BCRP were expressed in the conjunctival epithelium; MRP1-2, MRP6-7, MDR1, and LRP were expressed in the ICB; MRP1-3, MRP6-7, MDR1, and LRP were expressed in the retina; MRP1-3, MRP6-7, MDR1, and LRP were expressed in the HCEC; and MRP7, MDR1, LRP, and BCRP were expressed in the ARPE-19. This quantitative and systematic study of efflux transporters in normal ocular tissues and cell lines provides evidence of cross-ocular tissue transporter expression differences, implying that efflux transporter expression variability should be taken into consideration for better understanding of ocular pharmacokinetic and pharmacodynamic data.

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“…The mechanism which generates the MDR phenotype is complex. 1 Mechanisms include drug excretion, antiapoptosis, activity changes in drugmetabolizing enzymes such as serum glutathione S epoxide transferase (GST), topoisomerase II (TOPO II), protein kinase C (PKC), and reinforcement of recovery from DNA injury. However the major mechanism in the mediation of MDR was P-glycoprotein (P-gp, P170), a kind of transmembrane glycoprotein.…”

Section: Introductionmentioning

confidence: 99%

Effect of magnetic nanoparticles of Fe3O4 and 5-bromotetrandrine on reversal of multidrug resistance in K562/A02 leukemic cells

Cheng

Wu²,

Chen³

et al. 2009

IJN

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This study aims to evaluate the multidrug resistance (MDR) reversal activity by magnetic nanoparticles of Fe3O4 (MNPs-Fe3O4) and 5-bromotetrandrine (BrTet) MDR cell line K562/A02 solitarily or symphysially. The proliferation of K562 and K562/A02 cells and the cytotoxicity on peripheral blood mononuclear cells (PMBCs) were evaluated by MTT assay. Cellular accumulation of daunorubicin (DNR) was analyzed by flow cytometry. Real-time polymerase chain reaction and Western blotting analyses were performed to examine the mRNA and protein levels of mdr1, respectively. The results showed that the combination of MNPs-Fe3O4 and BrTet with effective concentrations significantly increased cytotoxicity against MDR cell line K562/A02. Both BrTet and MNPs-Fe3O4 increased the intracellular DNR accumulation in the K562/A02 cell line, and downregulated the level of mdr1 gene and expression of P-glycoprotein. Furthermore, the combination did not have significant cytotoxicity in PMBCs. We propose that MNPs-Fe3O4 conjugated with DNR and BrTet probably have synergetic effects on MDR reversal.

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Drug‐Metabolizing Enzymes and Transporters: Expression in the Human Prostate and Roles in Prostate Drug Disposition

Cited by 24 publications

References 116 publications

What makes the α_1A‐adrenoceptor gene product assume an α_1L‐adrenoceptor phenotype?

What makes the α_1A‐adrenoceptor gene product assume an α_1L‐adrenoceptor phenotype?

Expression of Efflux Transporters in Human Ocular Tissues

Effect of magnetic nanoparticles of Fe3O4 and 5-bromotetrandrine on reversal of multidrug resistance in K562/A02 leukemic cells

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Drug‐Metabolizing Enzymes and Transporters: Expression in the Human Prostate and Roles in Prostate Drug Disposition

Cited by 24 publications

References 116 publications

What makes the α1A‐adrenoceptor gene product assume an α1L‐adrenoceptor phenotype?

What makes the α1A‐adrenoceptor gene product assume an α1L‐adrenoceptor phenotype?

Expression of Efflux Transporters in Human Ocular Tissues

Effect of magnetic nanoparticles of Fe3O4 and 5-bromotetrandrine on reversal of multidrug resistance in K562/A02 leukemic cells

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Product

Resources

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What makes the α_1A‐adrenoceptor gene product assume an α_1L‐adrenoceptor phenotype?

What makes the α_1A‐adrenoceptor gene product assume an α_1L‐adrenoceptor phenotype?