ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2018
Lysophosphatidic acid and amitriptyline signal through LPA1R to reduce P-glycoprotein transport at the blood-brain barrier.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 23 citations in OpenAlex.
- The Antidepressant Amitriptyline Upregulates ERK1/2 Signaling and Inhibits Rho-Mediated Responses Induced by Lysophosphatidic Acid in Astroglial Cells.International journal of molecular sciences · 2026Article
- Autotaxin regulates the expression and the activity of P-glycoprotein in lipopolysaccharide -activated microglial cells.Cytotechnology · 2025Article
- Nongenomic ERα-AMPK Signaling Regulates Sex-Dependent Bcrp Transport Activity at the Blood-Brain Barrier.Endocrinology · 2024Article
- Expression and functions of adenylyl cyclases in the CNS.Fluids and barriers of the CNS · 2022Review
- Disease-Induced Modulation of Drug Transporters at the Blood-Brain Barrier Level.International journal of molecular sciences · 2021Review
- Activation of Macrophages by Lysophosphatidic Acid through the Lysophosphatidic Acid Receptor 1 as a Novel Mechanism in Multiple Sclerosis Pathogenesis.Molecular neurobiology · 2021Article
- Effect of GenX on P-Glycoprotein, Breast Cancer Resistance Protein, and Multidrug Resistance-Associated Protein 2 at the Blood-Brain Barrier.Environmental health perspectives · 2020Article
- Lysophosphatidic Acid Receptors: Biochemical and Clinical Implications in Different Diseases.Journal of Cancer · 2020Review
- Established and Emerging Strategies for Drug Delivery Across the Blood-Brain Barrier in Brain Cancer.Pharmaceutics · 2019Review
- Emerging role for SRC family kinases in junction dynamics during spermatogenesis.Reproduction (Cambridge, England) · 2019Review
- Acute pain alters P-glycoprotein-containing protein complexes in rat cerebral microvessels: Implications for P-glycoprotein trafficking.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The blood-brain barrier is a microvascular network that (1) provides neuroprotection from metabolic and environmental toxins and (2) limits the delivery of therapeutics to the central nervous system (CNS). The ATP-binding cassette transporter P-glycoprotein contributes to the latter by actively pumping clinical substrates back into circulation before they can reach the brain parenchyma. Targeting P-glycoprotein has proven effective in increasing the delivery of therapeutics to their cerebral targets. We provide a novel mechanism to achieve this end in functioning, intact rat brain capillaries, whereby the bioactive phospholipid lysophosphatidic acid (LPA) and tricyclic antidepressant (TCA) amitriptyline reduce basal P-glycoprotein transport activity through a distinct lysophosphatidic acid 1 receptor-mediated signaling cascade that requires G-protein coupling, Src kinase, and ERK 1/2. Furthermore, we demonstrate the ability of LPA and TCA amitriptyline to decrease induced P-glycoprotein transport activity in a human SOD1 transgenic rat model of amyotrophic lateral sclerosis. This work may translate to new clinical strategies for increasing the cerebral penetration of therapeutics in patients suffering from CNS diseases marked by exacerbated pharmacoresistance.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.