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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: ATP Binding Cassette Transporter, Subfamily B, Member 1, Age Factors, Antibody Specificity, Biological Transport, Active, Blood-Brain Barrier, Cells, Cultured, Coculture Techniques, Digoxin, Dose-Response Relationship, Drug, Endothelial Cells, Endothelin-1, Flow Cytometry, Fluorescent Antibody Technique, Humans, Models, Biological, Neuroglia.
user
Does endothelin-1 reduce p-glycoprotein transport activity in an in vitro model of human adult blood-brain barrier? Context: It is a huge challenge to understand the blood-brain barrier (BBB), which is a key element in neuroinflammation associated with many brain diseases. The BBB also regulates the passage of xenobiotics into the central nervous system (CNS), and therefore influences drug efficacy. This may be due to the presence of ATP binding cassette transporters such as P-glycoprotein (Pgp) on the BBB, which are efflux pumps known to transport many drugs. The peptide endothelin 1 (ET-1) is involved in different kinds of CNS diseases and neuroinflammation, and is known to modulate Pgp transport activity. Although there are data from animal models, data from human models are scarce. We evaluated Pgp expression and transport activity in adult human brain microvascular endothelial cells (HBMECs) when exposing an adult human in vitro BBB model to ET-1. Adult HBMECs were cocultured with human adult glial cells on a Transwells to mimic blood and CNS compartments. These human in vitro BBBs were exposed for 24 h to 100 nM and 10 nM ET-1. Pgp expression was assessed by flow cytometry and its transport activity by measuring radiolabelled digoxin passage. After exposure to ET-1, flow cytometry showed no shift of fluorescence intensity for a Pgp specific antibody. The passage of digoxin increased with a significant decrease of Q ratio for 10 nM ET-1.
assistant
Our results show that ET-1 has no effect on Pgp expression of adult HBMECs, but does modulate Pgp transport activity. Final Decision: yes