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

Vanilloid receptors (VRs) play a fundamental role in the transduction of pe ripheral tissue injury and/or inflammation responses. Molecules that antago nize VR channel activity may act as selective and potent analgesics, We rep ort that synthetic arginine-rich hexapeptides block heterologously expresse d VR-1 channels with submicromolar efficacy in a weak voltage-dependent man ner, consistent with a binding site located near/at the entryway of the aqu eous pore. Dynorphins, natural arginine-rich peptides, also blocked VR-1 ac tivity with micromolar affinity. Notably, synthetic and natural arginine-ri ch peptides attenuated the ocular irritation produced by topical capsaicin application onto the eyes of experimental animals. Taken together, our resu lts imply that arginine-rich peptides are VR-1 channel blockers with analge sic activity. These findings may expand the development of novel analgesics by targeting receptor sites distinct from the capsaicin binding site. (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Sc ience B.V, All rights reserved.