School of Biological Sciences, University of Auckland, Auckland, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland, New Zealand.
Headache Group, Wolfson Center for Age Related Diseases, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Trends Pharmacol Sci. 2023 Oct;44(10):651-663. doi: 10.1016/j.tips.2023.07.003. Epub 2023 Aug 3.
The neuropeptides calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide (PACAP) and their receptors are linked to migraine neurobiology. Recent antimigraine therapeutics targeting the signaling of these neuropeptides are effective; however, some patients respond suboptimally, indicating an incomplete understanding of migraine pathophysiology. The CGRP- and PACAP-responsive receptors can be differentially spliced. It is known that receptor splice variants can have different pathophysiological effects in other receptor-mediated pain pathways. Despite considerable knowledge on the structural and pharmacological differences of the CGRP- and PACAP-responsive receptor splice variants and their expression in migraine-relevant tissues, their role in migraine is rarely considered. Here we shine a spotlight on the calcitonin and PACAP (PAC) receptor splice variants and examine what implications they may have for drug activity and design.
降钙素基因相关肽（CGRP）和垂体腺苷酸环化酶激活肽（PACAP）及其受体与偏头痛的神经生物学有关。最近针对这些神经肽信号的抗偏头痛治疗方法是有效的；然而，一些患者的反应并不理想，这表明对偏头痛病理生理学的理解还不完全。CGRP 和 PACAP 反应性受体可以进行差异剪接。已知受体剪接变体在其他受受体调节的疼痛途径中可能具有不同的病理生理学作用。尽管对 CGRP 和 PACAP 反应性受体剪接变体的结构和药理学差异及其在偏头痛相关组织中的表达有了相当多的了解，但它们在偏头痛中的作用很少被考虑。在这里，我们重点介绍降钙素和 PACAP（PAC）受体剪接变体，并探讨它们对药物活性和设计可能产生的影响。
