Department of Physiology and Pharmacology Vittorio Erspamer, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
Curr Pharm Biotechnol. 2011 Oct;12(10):1720-7. doi: 10.2174/138920111798357410.
Bv8 is a small protein secreted by frog skin. Mammalian homologues of Bv8, the prokineticins PK1 and PK2, and their G-protein coupled receptors PKR1 and PKR2 have been identified and linked to several biological effects as gut motility, circadian rhythms, neurogenesis, angiogenesis and cancer progression, haematopoiesis and nociception. In rodents, administration of amphibian Bv8 lowers nociceptor thresholds to a broad spectrum of physical and chemical stimuli. The prokineticin receptors are present in regions of the nervous system associated with pain; primary sensitive neurons expressing PKRs also express the vanilloid receptor TRPV1, providing an anatomical basis for PKR1/TRPV1 cooperative interaction in nociceptor sensitization. Bv8/PK2, strongly up-regulated in neutrophils and other inflammatory cells, is a main pronociceptive mediator in inflamed tissues. Indeed Bv8/PK2 produced by inflammatory cells is released at the site of inflammation where it sensitizes peripheral nociceptors, stimulates chemotaxis and modulates the release of inflammatory and pronociceptive cytokines. Availability of a non-peptide PKR antagonist, leading to blockade the PK/PKR system, ameliorates pain arising from tissue injury and, additionally, reduces the time required for recovery from injury.
Bv8 是一种由青蛙皮肤分泌的小蛋白。哺乳动物同源物 Bv8、促动力素 PK1 和 PK2 及其 G 蛋白偶联受体 PKR1 和 PKR2 已被鉴定出来，并与多种生物学效应相关，如肠道运动、昼夜节律、神经发生、血管生成和癌症进展、造血和痛觉。在啮齿动物中，两栖类 Bv8 的给药会降低伤害感受器对广泛物理和化学刺激的阈值。促动力素受体存在于与疼痛相关的神经系统区域；表达 PKR 的初级敏感神经元也表达香草素受体 TRPV1，为 PKR1/TRPV1 在伤害感受器敏化中的协同相互作用提供了解剖学基础。Bv8/PK2 在中性粒细胞和其他炎症细胞中强烈上调，是炎症组织中主要的致痛介质。事实上，炎症细胞产生的 Bv8/PK2 会在炎症部位释放，从而使外周伤害感受器敏感化，刺激趋化作用，并调节炎症和致痛细胞因子的释放。非肽 PKR 拮抗剂的可用性导致 PK/PKR 系统被阻断，从而减轻组织损伤引起的疼痛，并减少从损伤中恢复所需的时间。
