Pharmacological evidence for the participation of NO-cyclic GMP-PKG-K+ channel pathway in the antiallodynic action of resveratrol.
The possible participation of the nitric oxide (NO)-cyclic GMP-protein kinase G (PKG)-K+ channels pathway in the antiallodynic action of resveratrol and YC-1 in spinal nerve injured rats was assessed. Ligation of L5/L6 spinal nerves produced a clear-cut tactile allodynia in the rats. Intrathecal administration of resveratrol (100-600 microg) and 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (0.1-2.7 microg, YC-1, a soluble guanylyl cyclase activator) decreased tactile allodynia induced by ligation of L5/L6 spinal nerves. Intrathecal treatment with NG-L-nitro-arginine methyl ester (10-100 microg, L-NAME, a NO synthase inhibitor), 1H-(1,2,4)-oxadiazolo(4,2-a)quinoxalin-1-one (1-10 microg, ODQ, a soluble guanylyl cyclase inhibitor), KT-5823 (5-500 ng, a PKG inhibitor) and iberiotoxin (5-500 ng, a large-conductance Ca2+ -activated K+ channel blocker), but not NG-D-nitro-arginine methyl ester (100 microg, D-NAME, an inactive isomer of L-NAME), glibenclamide (12.5-50 microg, ATP-sensitive K+ channel blocker) or vehicle, significantly diminished resveratrol (300 microg)- and YC-1 (2.7 microg)-induced spinal antiallodynia. These effects were independent of prostaglandin synthesis inhibition as indomethacin did not affect resveratrol-induced antiallodynia. Results suggest that resveratrol and YC-1 could activate the proteins of the NO-cyclic GMP-PKG spinal pathway or large-conductance Ca2+ -activated, but not ATP-sensitive, K+ channels at the spinal cord in order to produce at least part of their antiallodynic effect in this model of neuropathy.
Bermúdez-Ocaña
Deysi Y
DY
Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados, Sede Sur, México, D.F., Mexico.
Ambriz-Tututi
Mónica
M
Pérez-Severiano
Francisca
F
Granados-Soto
Vinicio
V
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000737:chemistry*; D010455:Peptides / Q000494:pharmacology; D011188:Potassium / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D013131:Spine / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*
D000975:Antioxidants; D010455:Peptides; D013267:Stilbenes; D009569:Nitric Oxide; C064719:iberiotoxin; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP; D000077185:Resveratrol; D011188:Potassium; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester