Introduction: ATP binding cassette (ABC) membrane transporter multidrug resistance 1 (MDR1) is one of the most important efflux transporters in the human placenta protecting the fetus from exposure to xenobiotic toxicity. Recent studies have focused on placental MDR1 expression, but few studies have analyzed placental MDR1 transport activity. The purpose of this study was to investigate placental MDR1 transport activity using a relatively large sample size of human placentas. Furthermore, the effect of ABCB1 gene polymorphisms were investigated along with physiological factors including maternal age, times of pregnancy, BMI, delivery mode or pregnancy complications on placental MDR1 transport activity.
Methods: A total of 252 human placentas were obtained after delivery. MDR1 transport activity was detected by N-methyl quinidine uptake in placental microvillus membrane vesicles (MVMVs). Nine common single nucleotide polymorphisms (SNPs) in ABCB1 genes were determined by Snapshot. The association between ABCB1 gene polymorphisms, maternal age, times of pregnancy, BMI, delivery mode or pregnancy complications, and transporter activity was investigated.
Results: Inter-individual variations of MDR1 transport activity were observed among 252 subjects. The per unit protein activity was ranged from 0.05 to 0.15/mg. Nine SNPs in ABCB1 gene didn't exhibit significant association with transporter activity of MDR1. Likewise, neither age, times of pregnancy, delivery mode nor pregnancy complications showed any significant effect of placental MDR1 transport activity. But placental MDR1 transport activity in obese pregnant women was lower than those in non-obese pregnant women.
Conclusion: Inter-individual variations of MDR1 transport activity existed in human placentas. This may contribute to variations in drug exposure to the fetus affecting clinical outcomes. Maternal age, times of pregnancy, delivery mode nor pregnancy complications included in this study maybe not significantly impact placental MDR1 transport activity, but maternal obese could inhibit placental MDR1 activity.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.placenta.2020.06.001 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Transporter Expressions as Part of Required Scaling Factor to Support In vitro In vivo Extrapolation for Blood-Brain Barrier Drug Permeability.
Eur J Pharm Sci
January 2025
Centre for Applied Pharmacokinetic Research, University of Manchester, UK.
Access of drugs to the central nervous system is limited by the blood-brain barrier, and this in turn affects drug efficacy/toxicity. To date, most drug discovery optimization paradigms have relied heavily on in vitro transporter assays and preclinical species pharmacokinetic evaluation to provide a qualitative assessment of human brain penetration. Because of the lack of human brain pharmacokinetic data, mechanistic models for preclinical species, combined with in vitro and in silico data, are useful for translation to human.
View Article and Find Full Text PDFStructural insights into binding-site access and ligand recognition by human ABCB1.
EMBO J
January 2025
The Hormel Institute, University of Minnesota, Austin, MN, 55912, USA.
ABCB1 is a broad-spectrum efflux pump central to cellular drug handling and multidrug resistance in humans. However, how it is able to recognize and transport a wide range of diverse substrates remains poorly understood. Here we present cryo-EM structures of lipid-embedded human ABCB1 in conformationally distinct apo-, substrate-bound, inhibitor-bound, and nucleotide-trapped states at 3.
View Article and Find Full Text PDFLow prevalence of copy number variation in pfmdr1 and pfpm2 in Plasmodium falciparum isolates from southern Angola.
Malar J
January 2025
Global Health and Tropical Medicine, GHTM, Associate Laboratory in Translation and Innovation Towards Global Health, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, UNL, Rua da Junqueira 100, 1349-008, Lisbon, Portugal.
Background: Malaria is the parasitic disease with the highest global morbidity and mortality. According to estimates from the World Health Organization (WHO), there were around 249 million cases in 2022, with 3.4% occurring in Angola.
View Article and Find Full Text PDFThe canine blood-brain barrier in health and disease: focus on brain protection.
Vet Q
December 2025
Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada.
This review examines the role of the canine blood-brain barrier (BBB) in health and disease, focusing on the impact of the multidrug resistance (MDR) transporter P-glycoprotein (P-gp) encoded by the gene. The BBB is critical in maintaining central nervous system homeostasis and brain protection against xenobiotics and environmental drugs that may be circulating in the blood stream. We revise key anatomical, histological and functional aspects of the canine BBB and examine the role of the gene mutation in specific dog breeds that exhibit reduced P-gp activity and disrupted drug brain pharmacokinetics.
View Article and Find Full Text PDFCross-resistance between strain AFS009 metabolites (Howler EVO) and fludioxonil in .
Plant Dis
January 2025
Clemson University, Entomology, Soils, and Plant Sciences, 120 Long Hall, Clemson, South Carolina, United States, 29634-0315;
Howler EVO is a biological fungicide based on metabolites of the bacterium Pseudomonas chlororaphis strain AFS009. One of the metabolites, pyrrolnitrin (PRN), is a chemical analogue of the phenylpyrrole fludioxonil used to manage gray mold of fruit crops caused by Botrytis cinerea. Resistance to fludioxonil in B.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!