Nociceptive sensitization by the secretory protein Bv8
Nociceptive sensitization by the secretory protein Bv8
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DOI：
10.1038/sj.bjp.0704995
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发表时间：
2002-12-01
影响因子：
7.3
通讯作者：
Melchiorri, P
中科院分区：
文献类型：
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作者：
Negri, L;Lattanzi, R;Melchiorri, P
1从两栖动物皮肤中分离得到的小蛋白Bv8属于一个新的分泌蛋白家族(Bv8-Prokineticin家族，Swiss-Prot：Q9PW66)，其同源基因在从无脊椎动物到人类的整个进化过程中都是保守的。2给大鼠静脉或皮下注射Bv8(从0.06到500pmokg(-1))或鞘内(从6fmo1到250pmo1)，Bv8对施加在尾巴和爪子上的机械和热刺激产生强烈的全身伤害性敏感性。大鼠背根神经节(DRG)、脊髓背侧象限(DSC)、结合Bv8的Bv8和哺乳动物直系同源基因EG-VEGF均表达两种G蛋白偶联的原激动素受体PK-R1和PK-R2。在DSC中，PK-R1比PK-R2更丰富，而两者在DRG中的表达相同。Bv8和EG-VEGF抑制[I-125]-Bv8与大鼠DRG和DSC结合的IC50分别为4.1+/-0.4 nmBv8和76.4+/-7.6 nmEG-VEGF，在DRG为7.3+/-0.9 nmBv8和330+/-41 nmEG-VEGF，在小直径神经元(<；6这些数据表明，Bv8通过与DSC和初级敏感神经元的PK受体结合，导致外周伤害性感受器对热和机械刺激的强烈敏化。
1 The small protein Bv8, isolated from amphibian skin, belongs to a novel family of secretory proteins (Bv8-Prokineticin family, SWISS-PROT: Q9PW66) whose orthologues have been conserved throughout evolution, from invertebrates to humans.2 When injected intravenously or subcutaneously (from 0.06 to 500 pmol kg(-1)) or intrathecally (from 6 fmol to 250 pmol) in rats, Bv8 produced an intense systemic nociceptive sensitization to mechanical and thermal stimuli applied to the tail and paws.3 Topically delivered into one rat paw, 50 fmol of Bv8 decreased by 50% the nociceptive threshold to pressure in the injected paw without affecting the threshold in the contralateral paw.4 The two G-protein coupled prokineticin receptors, PK-R1 and PK-R2, were expressed in rat dorsal root ganglia (DRG) and in dorsal quadrants of spinal cord (DSC) and bound Bv8 and the mammalian orthologue, EG-VEGF, with high affinity. In DSC, PK-R1 was more abundant than PK-R2, whereas both receptors were equally expressed in DRG. IC50 of Bv8 and EG-VEGF to inhibit [I-125]-Bv8 binding to rat DRG and DSC were 4.1 +/- 0.4 nM Bv8 and 76.4 +/- 7.6 nm EG-VEGF, in DRG; 7.3 +/- 0.9 nm Bv8 and 330 +/- 41 nm EG-VEGF, in DSC.5 In the small diameter neurons (< 30 pm) of rat DRG cultures, Bv8 concentrations, ranging from 0.2 to 10 nM, raised [Ca2+] in a dose-dependent manner.6 These data suggest that Bv8, through binding to PK receptors of DSC and primary sensitive neurons, results in intense sensitization of peripheral nociceptors to thermal and mechanical stimuli.