Arginine‐rich peptides are blockers of VR‐1 channels with analgesic activity

FEBS Letters

González-Ros, J.M.³  Merino, J.M.²  Belmonte, C.⁴  Planells-Cases, R.³  Aracil, A.⁴  Pérez-Payá, E.¹  Ferrer-Montiel, A.V.³  Gallar, J.⁴ 

[1] Departmento de Bioquı́mica y Biologı́a Molecular, Universidad de Valencia, Valencia, Spain;Departmento de Bioquı́mica y Biologı́a Molecular, Universidad de Extremadura, Badajoz, Spain;Centro de Biologı́a Molecular y Celular, Universidad Miguel Hernández, Edf. Torregaitán, Avda. Ferrocarril s/n, 03202 Elche (Alicante), Spain;Instituto de Neurosciencias, Universidad Miguel Hernández-CSIC, Alicante, Spain

关键词: Pain;    Nociceptor;    Capsaicin;    Dynorphin;    Non-competitive antagonist;    Ionic pore;   

DOI  :  10.1016/S0014-5793(00)01982-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown