Effects of 24-Hydroxycholesterol on the ATP-Induced Trigeminal Nerve Electrical Activity and the Mast Cells Degranulation

IF 1.1 Q4 CELL BIOLOGY
K. R. Gilizhdinova, D. A. Nurmieva, A. S. Ananev, A. M. Petrov, G. F. Sitdikova
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引用次数: 0

Abstract

The trigeminovascular system plays a pivotal role in the generation of nociceptive activity, which underlies pain in migraine and includes trigeminal nerve afferents, dura mater vessels, and mast cells. Adenosine triphosphate (ATP) is one of the main mediators of the interaction between vessels, nerve endings, and mast cells. ATP activates P2X3 receptors of trigeminal nerve afferents and P2X7 receptors of mast cells. 24-Hydroxycholesterol is the primary brain cholesterol metabolite synthesized by neurons and is capable of freely entering the bloodstream by crossing the blood–brain barrier. The purpose of this study was to examine the impact of 24-hydroxycholesterol on the electrical activity of trigeminal nerve afferents triggered by ATP application and on the mast cells degranulation in rat brain meninges. The electrical activity of the trigeminal nerve was recorded using an extracellular electrode in a rat hemiskull preparation, mast cells were stained with toluidine blue. 24-Hydroxycholesterol had no direct effect on the frequency of action potentials of trigeminal nerve but suppressed the response triggered by ATP application. Furthermore, incubation of meninges in 24-hydroxycholesterol resulted in a reduction in mast cell degranulation in response to ATP. Therefore, 24-hydroxycholesterol prevented the activation of trigeminal afferents either directly by reducing the activity of ionotropic ATP receptors or indirectly by stabilizing mast cells.

24-羟基胆固醇对atp诱导的三叉神经电活动和肥大细胞脱颗粒的影响
三叉神经血管系统在痛觉活动的产生中起关键作用,痛觉活动是偏头痛的基础,包括三叉神经传入神经、硬脑膜血管和肥大细胞。三磷酸腺苷(ATP)是血管、神经末梢和肥大细胞之间相互作用的主要介质之一。ATP激活三叉神经传入神经的P2X3受体和肥大细胞的P2X7受体。24-羟基胆固醇是脑内主要的胆固醇代谢物,由神经元合成,可通过血脑屏障自由进入血流。本研究的目的是研究24-羟基胆固醇对ATP触发的三叉神经传入神经电活动和对大鼠脑膜肥大细胞脱颗粒的影响。用细胞外电极记录三叉神经的电活动,在大鼠半颅骨制备中,肥大细胞用甲苯胺蓝染色。24-羟基胆固醇对三叉神经动作电位频率无直接影响,但抑制ATP的作用。此外,脑膜在24-羟基胆固醇中孵育导致肥大细胞脱颗粒减少,以响应ATP。因此,24-羟基胆固醇通过直接降低离子性ATP受体的活性或间接稳定肥大细胞来阻止三叉神经传入神经的激活。
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来源期刊
CiteScore
1.40
自引率
0.00%
发文量
28
期刊介绍: Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology   is an international peer reviewed journal that publishes original articles on physical, chemical, and molecular mechanisms that underlie basic properties of biological membranes and mediate membrane-related cellular functions. The primary topics of the journal are membrane structure, mechanisms of membrane transport, bioenergetics and photobiology, intracellular signaling as well as membrane aspects of cell biology, immunology, and medicine. The journal is multidisciplinary and gives preference to those articles that employ a variety of experimental approaches, basically in biophysics but also in biochemistry, cytology, and molecular biology. The journal publishes articles that strive for unveiling membrane and cellular functions through innovative theoretical models and computer simulations.
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