Akerman S, Kaube H, Goadsby P J
Headache Group, Institute of Neurology and National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK.
J Pharmacol Exp Ther. 2004 Apr;309(1):56-63. doi: 10.1124/jpet.103.059808. Epub 2004 Jan 12.
Arachidonylethanolamide (anandamide, AEA) is believed to be the endogenous ligand of the cannabinoid CB(1) and CB(2) receptors. CB(1) receptors have been found localized on fibers in the spinal trigeminal tract and spinal trigeminal nucleus caudalis. Known behavioral effects of anandamide are antinociception, catalepsy, hypothermia, and depression of motor activity, similar to Delta(9)-tetrahydocannanbinol, the psychoactive constituent of cannabis. It may be a possible therapeutic target for migraine. In this study, we looked at the possible role of the CB(1) receptor in the trigeminovascular system, using intravital microscopy to study the effects of anandamide against various vasodilator agents. Anandamide was able to inhibit dural blood vessel dilation brought about by electrical stimulation by 50%, calcitonin gene-related peptide (CGRP) by 30%, capsaicin by 45%, and nitric oxide by 40%. CGRP(8-37) was also able to attenuate nitric oxide (NO)-induced dilation by 50%. The anandamide inhibition was reversed by the CB(1) receptor antagonist AM251. Anandamide also reduced the blood pressure changes caused by CGRP injection, this effect was not reversed by AM251. It would seem that anandamide acts both presynaptically, to prevent CGRP release from trigeminal sensory fibers, and postsynaptically to inhibit the CGRP-induced NO release in the smooth muscle of dural arteries. CB(1) receptors seem to be involved in the NO/CGRP relationship that exists in causing headache and dural blood vessel dilation. It also seems that some of the blood pressure changes caused by anandamide are mediated by a noncannabinoid receptor, as AM251 was unable to reverse these effects. It can be suggested that anandamide is tonically released to play some form of modulatory role in the trigeminovascular system.
花生四烯酸乙醇胺（阿南达胺，AEA）被认为是大麻素CB(1)和CB(2)受体的内源性配体。已发现CB(1)受体定位于三叉神经脊髓束和三叉神经尾侧脊核的纤维上。阿南达胺已知的行为效应包括抗伤害感受、僵住症、体温过低以及运动活动抑制，类似于大麻的精神活性成分Δ9 - 四氢大麻酚。它可能是偏头痛的一个潜在治疗靶点。在本研究中，我们利用活体显微镜研究阿南达胺对各种血管扩张剂的作用，探讨CB(1)受体在三叉神经血管系统中的可能作用。阿南达胺能够将电刺激引起的硬脑膜血管扩张抑制50%，降钙素基因相关肽（CGRP）引起的抑制30%，辣椒素引起的抑制45%，一氧化氮引起的抑制40%。CGRP(8 - 37)也能够将一氧化氮（NO）诱导的扩张减弱50%。阿南达胺的抑制作用被CB(1)受体拮抗剂AM251逆转。阿南达胺还能降低CGRP注射引起的血压变化，这种效应未被AM251逆转。似乎阿南达胺在突触前起作用，阻止CGRP从三叉神经感觉纤维释放，在突触后抑制硬脑膜动脉平滑肌中CGRP诱导的NO释放。CB(1)受体似乎参与了在引起头痛和硬脑膜血管扩张中存在的NO/CGRP关系。似乎阿南达胺引起的一些血压变化是由非大麻素受体介导的，因为AM251无法逆转这些效应。可以推测，阿南达胺持续释放以在三叉神经血管系统中发挥某种形式的调节作用。
