Planells-Cases R, Aracil A, Merino J M, Gallar J, Pérez-Payá E, Belmonte C, González-Ros J M, Ferrer-Montiel A V
Centro de Biologia Molecular y Celular, Universidad Miguel Hernandez, Edf. Torregaitan, Avda, Ferrocarril sln, 03202 Elche, Spain.
FEBS Lett. 2000 Sep 15;481(2):131-6. doi: 10.1016/s0014-5793(00)01982-7.
Vanilloid receptors (VRs) play a fundamental role in the transduction of peripheral tissue injury and/or inflammation responses. Molecules that antagonize VR channel activity may act as selective and potent analgesics. We report that synthetic arginine-rich hexapeptides block heterologously expressed VR-1 channels with submicromolar efficacy in a weak voltage-dependent manner, consistent with a binding site located near/at the entryway of the aqueous pore. Dynorphins, natural arginine-rich peptides, also blocked VR-1 activity with micromolar affinity. Notably, synthetic and natural arginine-rich peptides attenuated the ocular irritation produced by topical capsaicin application onto the eyes of experimental animals. Taken together, our results imply that arginine-rich peptides are VR-1 channel blockers with analgesic activity. These findings may expand the development of novel analgesics by targeting receptor sites distinct from the capsaicin binding site.
香草酸受体（VRs）在转导外周组织损伤和/或炎症反应中起基本作用。拮抗VR通道活性的分子可能作为选择性强效镇痛药。我们报告，富含精氨酸的合成六肽以亚微摩尔效力、弱电压依赖性方式阻断异源表达的VR-1通道，这与位于水通道入口附近/处的结合位点一致。强啡肽，即天然富含精氨酸的肽，也以微摩尔亲和力阻断VR-1活性。值得注意的是，合成的和天然的富含精氨酸的肽减轻了将辣椒素局部应用于实验动物眼睛所产生的眼刺激。综上所述，我们的结果表明富含精氨酸的肽是具有镇痛活性的VR-1通道阻滞剂。这些发现可能通过靶向与辣椒素结合位点不同的受体位点来扩展新型镇痛药的开发。
