title: Quantitative PCR analysis and protein distribution of drug transporter genes in the rat cochlea.
abstract: Membrane transporters can be major determinants in the targeting and effectiveness of pharmaceutical agents. A large number of biologically important membrane transporters have been identified and localized to a variety of tissues, organs and cell types. However, little is known about the expression of key membrane transporters in the inner ear, a promising site for targeted therapeutics, as well as a region vulnerable to adverse drug reactions and environmental factors. In this study, we examined the levels of endogenous membrane transporters in rat cochlea by targeted PCR array analysis of 84 transporter genes, followed by validation and localization in tissues by immunohistochemistry. Our studies indicate that several members of the SLC, VDAC and ABC membrane transporter families show high levels of expression, both at the RNA and protein levels in the rat cochlea. Identification and characterization of these membrane transporters in the inner ear have clinical implications for both therapeutic and cytotoxic mechanisms that may aid in the preservation of auditory function.
authors.affiliation: Center for Hearing & Deafness, University at Buffalo, NY 14214, United States.
authors.forename: Senthilvelan
authors.initials: S
authors.lastname: Manohar
authors.affiliation: Center for Hearing & Deafness, University at Buffalo, NY 14214, United States.
authors.forename: Samson
authors.initials: S
authors.lastname: Jamesdaniel
authors.affiliation: Center for Hearing & Deafness, University at Buffalo, NY 14214, United States.
authors.forename: Dalian
authors.initials: D
authors.lastname: Ding
authors.affiliation: Center for Hearing & Deafness, University at Buffalo, NY 14214, United States.
authors.forename: Richard
authors.initials: R
authors.lastname: Salvi
authors.affiliation: Center for Hearing & Deafness, University at Buffalo, NY 14214, United States; SUNY Eye Institute, New York, United States.
authors.forename: Gail M
authors.initials: GM
authors.lastname: Seigel
authors.affiliation: Department of Pharmacology and Toxicology, University at Buffalo, NY 14214, United States. Electronic address: jaroth@buffalo.edu.
authors.forename: Jerome A
authors.initials: JA
authors.lastname: Roth
mesh_terms: D000818:Animals; D001692:Biological Transport; D003051:Cochlea / Q000378:metabolism*; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D026901:Membrane Transport Proteins; D004364:Pharmaceutical Preparations; D012333:RNA, Messenger
keywords: Cochlea; Immunohistochemistry; Membrane transporter; PCR array