跳转至内容
Merck
CN
  • Lysophosphatidic acid and amitriptyline signal through LPA1R to reduce P-glycoprotein transport at the blood-brain barrier.

Lysophosphatidic acid and amitriptyline signal through LPA1R to reduce P-glycoprotein transport at the blood-brain barrier.

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (2017-04-28)
David B Banks, Gary Ny Chan, Rebecca A Evans, David S Miller, Ronald E Cannon
摘要

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.

材料
货号
品牌
产品描述

Sigma-Aldrich
磺酰罗丹明 101, Dye content ~95 %
登录查看公司和协议定价
货号包装规格是否有货价格数量
100 μg
请联系客服了解存货情况
CN¥4,409.51
Sigma-Aldrich
PP2, ≥98% (HPLC)
登录查看公司和协议定价
货号包装规格是否有货价格数量
100 μg
请联系客服了解存货情况
CN¥4,409.51
Sigma-Aldrich
NAEPA, ≥98 (TLC), solid
登录查看公司和协议定价
货号包装规格是否有货价格数量
100 μg
请联系客服了解存货情况
CN¥4,409.51