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Due</p>\r\n<p>to high lipophilicity, cannabinoids can easily penetrate physiological barriers like</p>\r\n<p>the human placenta and jeopardize the developing fetus.We evaluated the impact</p>\r\n<p>of cannabidiol (CBD), a major non-psychoactive cannabinoid, on P-glycoprotein</p>\r\n<p>(P-gp) and Breast Cancer Resistance Protein (BCRP) expression, and P-gp function</p>\r\n<p>in a placental model, BeWo and Jar choriocarcinoma cell lines (using P-gp induced</p>\r\n<p>MCF7 cells (MCF7/P-gp) for comparison).</p>\r\n<p>Study design. Following the establishment of the basal expression of these transporters</p>\r\n<p>in the membrane fraction of all three cell lines, P-gp and BCRP protein</p>\r\n<p>and mRNA levels were determined following chronic (24–72 h) exposure to CBD,</p>\r\n<p>by Western Blot and qPCR. CBD impact on P-gp efflux function was examined</p>\r\n<p>by uptake of specific P-gp fluorescent substrates (calcein-AM, DiOC2(3) and rhodamine123(</p>\r\n<p>rh123)). Cyclosporine A (CsA) served as a positive control.</p>\r\n<p>Results. Chronic exposure to CBD resulted in significant changes in the protein and</p>\r\n<p>mRNA levels of both transporters. While P-gp was down-regulated, BCRP levels</p>\r\n<p>were up-regulated in the choriocarcinoma cell lines. CBD had a remarkably different</p>\r\n<p>influence on P-gp and BCRP expression in MCF7/P-gp cells, demonstrating that</p>\r\n<p>these are cell type specific effects. P-gp dependent efflux (of calcein, DiOC2(3) and</p>\r\n<p>rh123) was inhibited upon short-termexposure to CBD.</p>\r\n<p>Conclusions. Our study shows that CBD might alter P-gp and BCRP expression in</p>\r\n<p>the human placenta, and inhibit P-gp efflux function.We conclude that marijuana</p>\r\n<p>use during pregnancy may reduce placental protective functions and change its</p>\r\n<p>morphological and physiological characteristics.</p>","study.pubmedId":24058883,"study.embaseId":null,"study.croIdentifier":"Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev , Israel","study.croInformation":"Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev , Israel","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"A published report from the literature. 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Due</p>\r\n<p>to high lipophilicity, cannabinoids can easily penetrate physiological barriers like</p>\r\n<p>the human placenta and jeopardize the developing fetus.We evaluated the impact</p>\r\n<p>of cannabidiol (CBD), a major non-psychoactive cannabinoid, on P-glycoprotein</p>\r\n<p>(P-gp) and Breast Cancer Resistance Protein (BCRP) expression, and P-gp function</p>\r\n<p>in a placental model, BeWo and Jar choriocarcinoma cell lines (using P-gp induced</p>\r\n<p>MCF7 cells (MCF7/P-gp) for comparison).</p>\r\n<p>Study design. Following the establishment of the basal expression of these transporters</p>\r\n<p>in the membrane fraction of all three cell lines, P-gp and BCRP protein</p>\r\n<p>and mRNA levels were determined following chronic (24–72 h) exposure to CBD,</p>\r\n<p>by Western Blot and qPCR. CBD impact on P-gp efflux function was examined</p>\r\n<p>by uptake of specific P-gp fluorescent substrates (calcein-AM, DiOC2(3) and rhodamine123(</p>\r\n<p>rh123)). Cyclosporine A (CsA) served as a positive control.</p>\r\n<p>Results. Chronic exposure to CBD resulted in significant changes in the protein and</p>\r\n<p>mRNA levels of both transporters. While P-gp was down-regulated, BCRP levels</p>\r\n<p>were up-regulated in the choriocarcinoma cell lines. CBD had a remarkably different</p>\r\n<p>influence on P-gp and BCRP expression in MCF7/P-gp cells, demonstrating that</p>\r\n<p>these are cell type specific effects. P-gp dependent efflux (of calcein, DiOC2(3) and</p>\r\n<p>rh123) was inhibited upon short-termexposure to CBD.</p>\r\n<p>Conclusions. Our study shows that CBD might alter P-gp and BCRP expression in</p>\r\n<p>the human placenta, and inhibit P-gp efflux function.We conclude that marijuana</p>\r\n<p>use during pregnancy may reduce placental protective functions and change its</p>\r\n<p>morphological and physiological characteristics.</p>","study.pubmedId":24058883,"study.embaseId":null,"study.croIdentifier":"Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev , Israel","study.croInformation":"Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev , Israel","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"A published report from the literature. 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(ABCB1)","transporters.conceptId":null,"transporters.experiment_transporter_xref.experimentId":668,"transporters.experiment_transporter_xref.transporterId":11,"quantifiedMetabolites.id":null,"quantifiedMetabolites.name":null,"quantifiedMetabolites.unii":null,"quantifiedMetabolites.inChIKey":null,"quantifiedMetabolites.publicDescription":null,"quantifiedMetabolites.internalComment":null,"quantifiedMetabolites.conceptId":null,"quantifiedMetabolites.enantiomerOfId":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.com":null,"quantifiedMetabolites.experiment_quantified_metabolite_xref.exp":null,"study.id":137,"study.uid":"NPDI-1wiJBw","study.name":"Cannabidiol changes P-gp and BCRP expression in trophoblast cell lines.","study.napdiIdentifier":null,"study.overallSummary":"<p>Objectives.Marijuana is the most commonly used illicit drug during pregnancy. Due</p>\r\n<p>to high lipophilicity, cannabinoids can easily penetrate physiological barriers like</p>\r\n<p>the human placenta and jeopardize the developing fetus.We evaluated the impact</p>\r\n<p>of cannabidiol (CBD), a major non-psychoactive cannabinoid, on P-glycoprotein</p>\r\n<p>(P-gp) and Breast Cancer Resistance Protein (BCRP) expression, and P-gp function</p>\r\n<p>in a placental model, BeWo and Jar choriocarcinoma cell lines (using P-gp induced</p>\r\n<p>MCF7 cells (MCF7/P-gp) for comparison).</p>\r\n<p>Study design. Following the establishment of the basal expression of these transporters</p>\r\n<p>in the membrane fraction of all three cell lines, P-gp and BCRP protein</p>\r\n<p>and mRNA levels were determined following chronic (24–72 h) exposure to CBD,</p>\r\n<p>by Western Blot and qPCR. CBD impact on P-gp efflux function was examined</p>\r\n<p>by uptake of specific P-gp fluorescent substrates (calcein-AM, DiOC2(3) and rhodamine123(</p>\r\n<p>rh123)). Cyclosporine A (CsA) served as a positive control.</p>\r\n<p>Results. Chronic exposure to CBD resulted in significant changes in the protein and</p>\r\n<p>mRNA levels of both transporters. While P-gp was down-regulated, BCRP levels</p>\r\n<p>were up-regulated in the choriocarcinoma cell lines. CBD had a remarkably different</p>\r\n<p>influence on P-gp and BCRP expression in MCF7/P-gp cells, demonstrating that</p>\r\n<p>these are cell type specific effects. P-gp dependent efflux (of calcein, DiOC2(3) and</p>\r\n<p>rh123) was inhibited upon short-termexposure to CBD.</p>\r\n<p>Conclusions. Our study shows that CBD might alter P-gp and BCRP expression in</p>\r\n<p>the human placenta, and inhibit P-gp efflux function.We conclude that marijuana</p>\r\n<p>use during pregnancy may reduce placental protective functions and change its</p>\r\n<p>morphological and physiological characteristics.</p>","study.pubmedId":24058883,"study.embaseId":null,"study.croIdentifier":"Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev , Israel","study.croInformation":"Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev , Israel","study.dateStart":null,"study.dateEnd":null,"study.internalComment":"A published report from the literature. 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