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Drug Transporters at the Human Blood-Testis Barrier.
Hau, Raymond K; Wright, Stephen H; Cherrington, Nathan J.
Afiliação
  • Hau RK; College of Pharmacy, Department of Pharmacology & Toxicology (R.K.H., N.J.C.) and College of Medicine, Department of Physiology (S.H.W.), The University of Arizona, Tucson, Arizona.
  • Wright SH; College of Pharmacy, Department of Pharmacology & Toxicology (R.K.H., N.J.C.) and College of Medicine, Department of Physiology (S.H.W.), The University of Arizona, Tucson, Arizona.
  • Cherrington NJ; College of Pharmacy, Department of Pharmacology & Toxicology (R.K.H., N.J.C.) and College of Medicine, Department of Physiology (S.H.W.), The University of Arizona, Tucson, Arizona cherring@pharmacy.arizona.edu.
Drug Metab Dispos ; 51(5): 560-571, 2023 05.
Article em En | MEDLINE | ID: mdl-36732077
Transporters are involved in the movement of many physiologically important molecules across cell membranes and have a substantial impact on the pharmacological and toxicological effect of xenobiotics. Many transporters have been studied in the context of disposition to, or toxicity in, organs such as the kidney and liver; however, transporters in the testes are increasingly gaining recognition for their role in drug transport across the blood-testis barrier (BTB). The BTB is an epithelial membrane barrier formed by adjacent Sertoli cells (SCs) in the seminiferous tubules that form intercellular junctional complexes to protect developing germ cells from the external environment. Consequently, many charged or large polar molecules cannot cross this barrier without assistance from a transporter. SCs express a variety of drug uptake and efflux transporters to control the flux of endogenous and exogenous molecules across the BTB. Recent studies have identified several transport pathways in SCs that allow certain drugs to circumvent the human BTB. These pathways may exist in other species, such as rodents and nonhuman primates; however, there is (1) a lack of information on their expression and/or localization in these species, and (2) conflicting reports on localization of some transporters that have been evaluated in rodents compared with humans. This review outlines the current knowledge on the expression and localization of pharmacologically relevant drug transporters in human testes and calls attention to the insufficient and contradictory understanding of testicular transporters in other species that are commonly used in drug disposition and toxicity studies. SIGNIFICANCE STATEMENT: While the expression, localization, and function of many xenobiotic transporters have been studied in organs such as the kidney and liver, the characterization of transporters in the testes is scarce. This review summarizes the expression and localization of common pharmacologically-relevant transporters in human testes that have significant implications for the development of drugs that can cross the blood-testis barrier. Potential expression differences between humans and rodents highlighted here suggest rodents may be inappropriate for some testicular disposition and toxicity studies.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Testículo / Barreira Hematotesticular Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Testículo / Barreira Hematotesticular Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2023 Tipo de documento: Article