Activation of ATP-sensitive K(+) channels: mechanism of peripheral antinociceptive action of the nitric oxide donor, sodium nitroprusside.
Using the rat paw pressure test, in which sensitivity is increased by intraplantar 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 the nitric oxide donor sodium nitroprusside (SNP). SNP elicited a dose-dependent (250 and 500 microgram/paw) peripheral antinociceptive effect, which was considered local, since only higher doses produced an effect in the contralateral paw. The effect of SNP (500 microgram/paw) was dose-dependently antagonized by intraplantar administration of the sulfonylureas tolbutamide (20, 40 and 160 microgram) and glibenclamide (40, 80 and 160 microgram), selective blockers of ATP-sensitive K(+) channels. Charybdotoxin (2 microgram/paw), a selective blocker of high conductance Ca(2+)-activated K(+) channels, and apamin (10 microgram/paw), a selective blocker of low conductance Ca(2+)-activated K(+) channels, did not modify the peripheral antinociception induced by SNP. Tetraethylammonium (2 mg/paw), 4-aminopyridine (200 microgram/paw) and cesium (800 microgram/paw) also had no effect. Based on this experimental evidence, we conclude that the activation of ATP-sensitive K(+) channels could be the mechanism by which nitric oxide, donated by SNP, induces peripheral antinociception, and that Ca(2+)-activated K(+) channels and voltage-dependent K(+) channels appear not to be involved in the process.
Soares
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Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Av. Antônio Carlos, 6627, Campus da Pampulha, CEP: 31.270.100, Minas Gerais, Belo Horizonte, Brazil.
Leite
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Tatsuo
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Duarte
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ID
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D018999:Charybdotoxin / Q000494:pharmacology; D006152:Cyclic GMP / Q000502:physiology; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D005996:Nitroglycerin / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D014044:Tolbutamide / Q000494:pharmacology*
D018712:Analgesics, Non-Narcotic; D020030:Nitric Oxide Donors; D015221:Potassium Channels; D018999:Charybdotoxin; D009599:Nitroprusside; D001030:Apamin; D000255:Adenosine Triphosphate; D014044:Tolbutamide; D005996:Nitroglycerin; D006152:Cyclic GMP; D015232:Dinoprostone