Ac. Soares et al., Activation of ATP-sensitive K+ channels: mechanism of peripheral antinociceptive action of the nitric oxide donor, sodium nitroprusside, EUR J PHARM, 400(1), 2000, pp. 67-71
Using the rat paw pressure test, in which sensitivity is increased by intra
plantar injection of prostaglandin E-2 (PGE(2)), we conducted a study using
several K+ channel blockers. The objective was to determine what types of
K+ channels could be involved in the peripheral antinociceptive action of t
he nitric oxide donor sodium nitroprusside (SNP). SNP elicited a dose-depen
dent (250 and 500 mu g/paw) peripheral antinociceptive effect, which was co
nsidered local, since only higher doses produced an effect in the contralat
eral paw. The effect of SNP (500 mu g/paw) was dose-dependently antagonized
by intraplantar administration of the sulfonylureas tolbutamide (20, 40 an
d 160 mu g) and glibenclamide (40, 80 and 160 mu g), selective blockers of
ATP-sensitive K+ channels. Charybdotoxin (2 mu g/paw), a selective blocker
of high conductance Ca2+-activated K+ channels, and apamin (10 mu g/paw), a
selective blocker of low conductance Ca2+-activated K+ channels, did not m
odify the peripheral antinociception induced by SNP. Tetraethylammonium (2
mg/paw), 4-aminopyridine (200 mu g/paw) and cesium(800 mu g/paw) also had n
o effect. Based on this experimental evidence, we conclude that the activat
ion of ATP-sensitive K+ channels could be the mechanism by which nitric oxi
de, donated by SNP, induces peripheral antinociception, and that Ca2+-activ
ated K+ channels and voltage-dependent K+ channels appear not to be involve
d in the process. (C) 2000 Elsevier Science B.V. All rights reserved.