title: Cellular Models and In Vitro Assays for the Screening of modulators of P-gp, MRP1 and BCRP.
abstract: Adenosine triphosphate (ATP)-binding cassette (ABC) transporters are highly expressed in tumor cells, as well as in organs involved in absorption and secretion processes, mediating the ATP-dependent efflux of compounds, both endogenous substances and xenobiotics, including drugs. Their expression and activity levels are modulated by the presence of inhibitors, inducers and/or activators. In vitro, ex vivo and in vivo studies with both known and newly synthesized P-glycoprotein (P-gp) inducers and/or activators have shown the usefulness of these transport mechanisms in reducing the systemic exposure and specific tissue access of potentially harmful compounds. This article focuses on the main ABC transporters involved in multidrug resistance [P-gp, multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP)] expressed in tissues of toxicological relevance, such as the blood-brain barrier, cardiovascular system, liver, kidney and intestine. Moreover, it provides a review of the available cellular models, in vitro and ex vivo assays for the screening and selection of safe and specific inducers and activators of these membrane transporters. The available cellular models and in vitro assays have been proposed as high throughput and low-cost alternatives to excessive animal testing, allowing the evaluation of a large number of compounds.
authors.affiliation: UCIBIO/REQUIMTE, Laboratório de Toxicologia, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal. mariline.gameiro@gmail.com.
authors.forename: Mariline
authors.initials: M
authors.lastname: Gameiro
authors.affiliation: UCIBIO/REQUIMTE, Laboratório de Toxicologia, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal. rsilva@ff.up.pt.
authors.forename: Renata
authors.initials: R
authors.lastname: Silva
authors.affiliation: UCIBIO/REQUIMTE, Laboratório de Toxicologia, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal. mcamorim@ff.up.pt.
authors.forename: Carolina
authors.initials: C
authors.lastname: Rocha-Pereira
authors.affiliation: UCIBIO/REQUIMTE, Laboratório de Toxicologia, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal. helenacarmo@ff.up.pt.
authors.forename: Helena
authors.initials: H
authors.lastname: Carmo
authors.affiliation: UCIBIO/REQUIMTE, Laboratório de Toxicologia, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal. felixdc@ff.up.pt.
authors.forename: Félix
authors.initials: F
authors.lastname: Carvalho
authors.affiliation: UCIBIO/REQUIMTE, Laboratório de Toxicologia, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal. mlbastos@ff.up.pt.
authors.forename: Maria de Lourdes
authors.initials: ML
authors.lastname: Bastos
authors.affiliation: UCIBIO/REQUIMTE, Laboratório de Toxicologia, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal. remiao@ff.up.pt.
authors.forename: Fernando
authors.initials: F
authors.lastname: Remião
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry / Q000378:metabolism*; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004351:Drug Resistance / Q000187:drug effects*; D006801:Humans; D008954:Models, Biological; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000737:chemistry / Q000378:metabolism*; D009928:Organ Specificity; D013329:Structure-Activity Relationship
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C421109:multidrug resistance-associated protein 1
keywords: ATP-binding cassette transporters; P-glycoprotein; activators; breast cancer resistance protein; cell-based assays; cellular models; in vitro assays; inducers; membrane assays; multidrug resistance-associated protein 1