Peroutka Stephen J
Synergia Pharma, Inc., 601 Gateway Boulevard, Suite 350, South San Francisco, CA 94080, USA.
Mol Interv. 2005 Oct;5(5):304-11. doi: 10.1124/mi.5.5.10.
Significant recent advances in molecular pharmacology have elucidated the molecular pathways involved in neurogenic inflammation (NI). The release of tachykinins and endothelin-3 (ET-3) from trigeminal neurons induces dural vascular permeability and vasodilatation via activation of tachykinin receptor 1 (Tacr1) and endothelin receptor type B (Ednrb) on endothelial cells. Endothelial cell receptor stimulation results in cellular contraction, leading to plasma protein extravasation (PPE), which is the most recognized physiological hallmark of NI, and nitric oxide-induced vasodilatation. By contrast, the release of calcitonin gene-related peptide (CGRP) from trigeminal neurons--also a key physiological component of NI--does not affect vascular permeability but does induce neurogenic vasodilatation (NV) via the direct, (i.e., endothelium-independent) relaxation of vascular smooth muscle. The molecular pharmacology of NI is discussed within the context of migraine research and assesses the putative role of the two key physiological components of NI (i.e., PPE and NV) in migraine pathophysiology. The data indicate that the PPE component of NI plays no significant role in migraine but that NV is likely to be involved in migraine pathophysiology.
近期分子药理学取得了重大进展，阐明了神经源性炎症（NI）所涉及的分子途径。三叉神经元释放速激肽和内皮素-3（ET-3），通过激活内皮细胞上的速激肽受体1（Tacr1）和B型内皮素受体（Ednrb），诱导硬脑膜血管通透性增加和血管扩张。内皮细胞受体受到刺激会导致细胞收缩，进而引起血浆蛋白外渗（PPE），这是NI最公认的生理标志，同时还会引发一氧化氮诱导的血管扩张。相比之下，三叉神经元释放的降钙素基因相关肽（CGRP）——也是NI的关键生理成分——并不影响血管通透性，但会通过直接（即不依赖内皮）使血管平滑肌舒张，从而诱导神经源性血管扩张（NV）。本文在偏头痛研究的背景下讨论了NI的分子药理学，并评估了NI的两个关键生理成分（即PPE和NV）在偏头痛病理生理学中的假定作用。数据表明，NI的PPE成分在偏头痛中不起重要作用，但NV可能参与偏头痛的病理生理学过程。
