Arginine-rich peptides are blockers of VR-1 channels with analgesic activity.
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.
Planells-Cases
R
R
Centro de Biologia Molecular y Celular, Universidad Miguel Hernandez, Edf. Torregaitan, Avda, Ferrocarril sln, 03202 Elche, Spain.
Aracil
A
A
Merino
J M
JM
Gallar
J
J
Pérez-Payá
E
E
Belmonte
C
C
González-Ros
J M
JM
Ferrer-Montiel
A V
AV
D000595:Amino Acid Sequence; D000700:Analgesics / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000032:analysis*; D002211:Capsaicin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004399:Dynorphins / Q000494:pharmacology; D004553:Electric Conductivity; D005123:Eye / Q000187:drug effects / Q000503:physiopathology; D020128:Inhibitory Concentration 50; D051379:Mice; D009865:Oocytes; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D011955:Receptors, Drug / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D050916:TRPV Cation Channels; D014982:Xenopus laevis
D000700:Analgesics; D010455:Peptides; D011955:Receptors, Drug; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D004399:Dynorphins; D001120:Arginine; D002211:Capsaicin