Targeting VIP and PACAP Receptor Signaling: New Insights into Designing Drugs for the PACAP Subfamily of Receptors.
Targeting VIP and PACAP Receptor Signaling: New Insights into Designing Drugs for the PACAP Subfamily of Receptors.
复制标题
靶向VIP和PACAP受体信号：为PACAP受体亚家族设计药物的新见解。
DOI：
10.3390/ijms23158069
复制
发表时间：
2022-07-22
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
腺苷酸环化酶激活肽（PACAP）和血管活性肠肽（VIP）是通过激活B1类G蛋白偶联受体（GPCR）的PACAP亚家族参与多种生理和病理过程的神经肽：VIP受体1（VPAC 1R）、VIP受体2（VPAC 2R）和PACAP I型受体（PAC 1R）。VIP和PACAP共享近70%的氨基酸序列同一性，而它们的受体PAC1R、VPAC1R和VPAC2R在受体的跨膜区域中共享60%的同源性。PACAP以高亲和力结合所有三种受体，而VIP以高亲和力结合VPAC1R和VPAC2R，并且与PACAP相比对PAC1R的亲和力低一千倍。由于VIP和PACAP受体在体内的广泛分布，靶向这些受体的药物的潜在治疗应用以及预期的不期望的副作用是众多的。由于这些受体的结构相似性，设计靶向这些受体的选择性治疗剂仍然具有挑战性。这篇综述讨论了最近发现的分子机制参与的选择性和信号的PACAP亚家族的受体，和未来的考虑，治疗靶向。
Pituitary Adenylate Cyclase-Activating Peptide (PACAP) and Vasoactive Intestinal Peptide (VIP) are neuropeptides involved in a diverse array of physiological and pathological processes through activating the PACAP subfamily of class B1 G protein-coupled receptors (GPCRs): VIP receptor 1 (VPAC1R), VIP receptor 2 (VPAC2R), and PACAP type I receptor (PAC1R). VIP and PACAP share nearly 70% amino acid sequence identity, while their receptors PAC1R, VPAC1R, and VPAC2R share 60% homology in the transmembrane regions of the receptor. PACAP binds with high affinity to all three receptors, while VIP binds with high affinity to VPAC1R and VPAC2R, and has a thousand-fold lower affinity for PAC1R compared to PACAP. Due to the wide distribution of VIP and PACAP receptors in the body, potential therapeutic applications of drugs targeting these receptors, as well as expected undesired side effects, are numerous. Designing selective therapeutics targeting these receptors remains challenging due to their structural similarities. This review discusses recent discoveries on the molecular mechanisms involved in the selectivity and signaling of the PACAP subfamily of receptors, and future considerations for therapeutic targeting.
影响因子：
3.7
作者：
Yin J;Wang L;Yin N;Tabuchi A;Kuppe H;Wolff G;Kuebler WM
通讯作者：
Kuebler WM
影响因子：
3.7
作者：
Yu R;Cui Z;Li M;Yang Y;Zhong J
通讯作者：
Zhong J
影响因子：
3.7
作者：
Kumar S;Pioszak A;Zhang C;Swaminathan K;Xu HE
通讯作者：
Xu HE