Bv8/PK2 and prokineticin receptors: a druggable pronociceptive system
Bv8/PK2 and prokineticin receptors: a druggable pronociceptive system
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DOI：
10.1016/j.coph.2011.10.023
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发表时间：
2012-02-01
影响因子：
4
通讯作者：
Lattanzi, Roberta
中科院分区：
文献类型：
--
作者：
Negri, Lucia;Lattanzi, Roberta
哺乳动物Bv 8（也称为prokineticin 2）是一种分泌蛋白，调节包括疼痛感知在内的多种生物过程。它属于一个新的趋化因子家族，激活两个G蛋白连接的受体（前动力蛋白受体1和2，PKR 1和PKR 2），在与疼痛相关的神经系统区域和参与免疫炎症反应的细胞中表达。初级敏感神经元共表达PKR和瞬时电位受体香草酸1，在伤害感受器敏化中合作。Bv 8在中性粒细胞和其他炎性细胞中强烈上调，是发炎组织中的主要伤害感受介质，其中它使外周伤害感受器敏感，刺激中性粒细胞趋化性并调节炎性和伤害感受细胞因子的释放。非肽PKR拮抗剂的可用性，导致Bv 8/PKR系统的阻断，减轻了组织损伤引起的疼痛，并减少了从损伤中恢复所需的时间。
Mammalian Bv8 (also called prokineticin 2) is a secreted protein that regulates diverse biological processes including pain perception. It belongs to a new family of chemokines, which activate two G-protein linked receptors (prokineticin receptor 1 and 2, PKR1 and PKR2) expressed in regions of the nervous system associated with pain and in cells participating to immuno-inflammatory responses. Primary sensitive neurons co-express PKRs and the transient potential receptor vanilloid 1, cooperating in nociceptor sensitization. Bv8, strongly upregulated in neutrophils and other inflammatory cells, is a main pronociceptive mediator in inflamed tissues, where it sensitizes peripheral nociceptors, stimulates neutrophil chemotaxis and modulates the release of inflammatory and pronociceptive cytokines. Availability of a nonpeptide PKR antagonist, leading to blockade of the Bv8/PKR system, ameliorates pain arising from tissue injury and reduces the time required for recovery from injury.