CGRP physiology, pharmacology, and therapeutic targets: migraine and beyond.

IF 29.9 1区 医学 Q1 PHYSIOLOGY
Physiological reviews Pub Date : 2023-04-01 Epub Date: 2022-12-01 DOI:10.1152/physrev.00059.2021
Andrew F Russo, Debbie L Hay
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引用次数: 0

Abstract

Calcitonin gene-related peptide (CGRP) is a neuropeptide with diverse physiological functions. Its two isoforms (α and β) are widely expressed throughout the body in sensory neurons as well as in other cell types, such as motor neurons and neuroendocrine cells. CGRP acts via at least two G protein-coupled receptors that form unusual complexes with receptor activity-modifying proteins. These are the CGRP receptor and the AMY1 receptor; in rodents, additional receptors come into play. Although CGRP is known to produce many effects, the precise molecular identity of the receptor(s) that mediates CGRP effects is seldom clear. Despite the many enigmas still in CGRP biology, therapeutics that target the CGRP axis to treat or prevent migraine are a bench-to-bedside success story. This review provides a contextual background on the regulation and sites of CGRP expression and CGRP receptor pharmacology. The physiological actions of CGRP in the nervous system are discussed, along with updates on CGRP actions in the cardiovascular, pulmonary, gastrointestinal, immune, hematopoietic, and reproductive systems and metabolic effects of CGRP in muscle and adipose tissues. We cover how CGRP in these systems is associated with disease states, most notably migraine. In this context, we discuss how CGRP actions in both the peripheral and central nervous systems provide a basis for therapeutic targeting of CGRP in migraine. Finally, we highlight potentially fertile ground for the development of additional therapeutics and combinatorial strategies that could be designed to modulate CGRP signaling for migraine and other diseases.

CGRP 生理、药理和治疗目标:偏头痛及其他。
降钙素基因相关肽(CGRP)是一种具有多种生理功能的神经肽。它的两种异构体(α 和 β)在全身的感觉神经元以及运动神经元和神经内分泌细胞等其他类型的细胞中广泛表达。CGRP 至少通过两种 G 蛋白偶联受体发挥作用,这两种受体与受体活性修饰蛋白形成不寻常的复合物。这两种受体是 CGRP 受体和 AMY1 受体;在啮齿类动物中,还有其他受体发挥作用。尽管已知 CGRP 可产生多种效应,但介导 CGRP 效应的受体的确切分子特征却很少明确。尽管 CGRP 生物学仍存在许多谜团,但以 CGRP 轴为靶点治疗或预防偏头痛的疗法已成为从实验室到临床的成功典范。本综述介绍了 CGRP 表达的调节和部位以及 CGRP 受体药理学的背景。文章讨论了 CGRP 在神经系统中的生理作用,以及 CGRP 在心血管、肺、胃肠道、免疫、造血和生殖系统中的最新作用,以及 CGRP 在肌肉和脂肪组织中的代谢作用。我们将介绍 CGRP 在这些系统中如何与疾病状态相关联,其中最显著的是偏头痛。在此背景下,我们将讨论 CGRP 在外周和中枢神经系统中的作用如何为偏头痛的 CGRP 靶向治疗提供基础。最后,我们强调了开发其他疗法和组合策略的潜在沃土,这些疗法和策略可用于调节偏头痛和其他疾病的 CGRP 信号。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Physiological reviews
Physiological reviews 医学-生理学
CiteScore
56.50
自引率
0.90%
发文量
53
期刊介绍: Physiological Reviews is a highly regarded journal that covers timely issues in physiological and biomedical sciences. It is targeted towards physiologists, neuroscientists, cell biologists, biophysicists, and clinicians with a special interest in pathophysiology. The journal has an ISSN of 0031-9333 for print and 1522-1210 for online versions. It has a unique publishing frequency where articles are published individually, but regular quarterly issues are also released in January, April, July, and October. The articles in this journal provide state-of-the-art and comprehensive coverage of various topics. They are valuable for teaching and research purposes as they offer interesting and clearly written updates on important new developments. Physiological Reviews holds a prominent position in the scientific community and consistently ranks as the most impactful journal in the field of physiology.
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