第二个信使信号绕过CGRP受体阻塞,在人类中引起偏头痛发作
Thien Phu Do1,2, Christina Deligianni1, Sarkhan Amirguliyev1
1Department of Neurology, Danish Headache Center, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
Brain : a journal of neurology
|August 4, 2023
概括
偏头痛发作可以由循环腺单酸盐 (cAMP) 机制触发,即使素基因相关 (CGRP) 受体被阻止. 这表明CGRP受体激活对于所有cAMP引起的偏头痛发作并非必不可少.
科学领域:
- 神经科学是一个神经科学.
- 药理学 药理学是指药理学的学科.
- 临床医学 临床医学
背景情况:
- 素基因相关 (CGRP) 与偏头痛病理生理学有关.
- CGRP信号传递涉及内血管光滑肌细胞中的循环腺单酸盐 (cAMP).
- 人类偏头痛中cAMP信号的CGRP受体激活的必要性尚不清楚.
研究的目的:
- 为了调查细胞内cAMP信号是否需要CGRP受体激活在人类的偏头痛发作期间.
- 为了确定cAMP介导的偏头痛发作是否可以独立于CGRP受体信号传递而引起.
主要方法:
- 进行了一项随机,双盲,安慰剂控制,并行试验.
- 一个人类偏头痛诱发模型涉及给人CGRP和西洛斯塔.
- 患有偏头痛的参与者接受了先前治疗的 erenumab (CGRP受体对抗剂) 或安慰剂.
主要成果:
- 偏头痛发作是由使用西洛斯塔的cAMP介导机制引起的,而不考虑erenumab对CGRP受体的阻断.
- 基洛斯塔诱导的头骨动脉扩张不受CGRP受体阻塞的影响.
- 临床证据表明,cAMP引起的偏头痛发作可以在没有CGRP受体激活的情况下发生.
结论:
- 偏头痛发作可以通过独立于CGRP受体激活的cAMP介导途径启动.
- 这一发现挑战了所有偏头痛发作中CGRP受体信号传递的普遍要求.
- 开辟了针对cAMP通路的基于机制的新型偏头痛治疗方法的道路.
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