| Sertraline alters multidrug resistance phosphoglycoprotein activity in the mouse placenta and fetal blood-brain barrier. | |
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MedLine Citation:
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PMID: 22510699 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Phosphoglycoprotein (P-gp) is highly expressed in the placental syncytiotrophoblast and prevents xenobiotics from entering the fetus. In tumor cells, P-gp-mediated substrate efflux is inhibited by selective serotonin reuptake inhibitors (SSRIs). However, nothing is known regarding the effects of SSRIs on P-gp function in the placenta or fetal tissues. We hypothesized that the SSRI sertraline would decrease P-gp-mediated drug efflux at the placenta and fetal blood-brain barrier (BBB)-increasing P-gp substrate transfer from the mother to the fetus and fetal brain. In contrast to our hypothesis, this study presents the novel findings that sertraline (4 hours exposure) increases placental P-gp-mediated efflux (P < .001), resulting in decreased drug transfer to the fetus. Meanwhile, sertraline decreases fetal (P < .001) and maternal (P < .05) BBB P-gp-mediated efflux, resulting in increased drug transfer into the fetal and maternal brain from the circulation. This suggests that P-gp regulation by sertraline is tissue specific. These findings have important clinical implications with respect to fetal protection during maternal drug therapy in pregnancy. |
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Authors:
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Manzerul Bhuiyan; Sophie Petropoulos; William Gibb; Stephen G Matthews |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Reproductive sciences (Thousand Oaks, Calif.) Volume: 19 ISSN: 1933-7205 ISO Abbreviation: Reprod Sci Publication Date: 2012 Apr |
Date Detail:
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Created Date: 2012-04-18 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101291249 Medline TA: Reprod Sci Country: United States |
Other Details:
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Languages: eng Pagination: 407-15 Citation Subset: IM |
Affiliation:
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1Department of Physiology, University of Toronto, Toronto , Canada. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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