Wang Yan, Li Yanli, Wang Minyan
Centre for Neuroscience, Xi'an Jiaotong-Liverpool University, Suzhou, PR China.
Centre for Neuroscience, Xi'an Jiaotong-Liverpool University, Suzhou, PR China; Department of Biological Sciences, Xi'an Jiaotong-Liverpool University, Suzhou, PR China.
Pharmacol Rep. 2016 Oct;68(5):935-8. doi: 10.1016/j.pharep.2016.05.001. Epub 2016 Jun 27.
Cortical spreading depression (CSD) is a transient propagating excitation of synaptic activity followed by depression, which is implicated in migraine with aura and is regarded as the underlying cause of migraine. Calcitonin-gene related peptide (CGRP) receptors play a crucial role in mediating the magnitude of CSD in rat cortical slice. This study aimed to examine whether CGRP receptors are involved in retinal spreading depression (RSD) in chicks.
Western blot was used for detection of calcitonin-receptor like receptor (CALCRL) and intrinsic optical imaging was used for pharmacological investigation.
We found that the key component of CGRP receptor, CALCRL, is expressed in the chick retina. Using an in vitro migraine RSD model, we demonstrated that BIBN4096, a potent antagonist for CGRP receptors, markedly reduced the magnitude of RSD induced by K(+), but also the propagation rate.
The data suggest that CGRP receptors mediate RSD propagation involving neuronal mechanism and approve that RSD is an efficient in vitro approach for assessing anti-migraine drugs targeting CGRP receptors.
皮层扩散性抑制（CSD）是一种突触活动的短暂传播性兴奋，随后出现抑制，与偏头痛伴先兆有关，被认为是偏头痛的潜在病因。降钙素基因相关肽（CGRP）受体在介导大鼠皮层切片中CSD的程度方面起关键作用。本研究旨在探讨CGRP受体是否参与雏鸡视网膜扩散性抑制（RSD）。
采用蛋白质免疫印迹法检测降钙素受体样受体（CALCRL），并采用内在光学成像进行药理学研究。
我们发现CGRP受体的关键成分CALCRL在雏鸡视网膜中表达。使用体外偏头痛RSD模型，我们证明CGRP受体的强效拮抗剂BIBN4096显著降低了由钾离子（K⁺）诱导的RSD的程度，同时也降低了传播速率。
数据表明CGRP受体介导RSD传播，涉及神经元机制，并证实RSD是评估靶向CGRP受体的抗偏头痛药物的有效体外方法。
