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Dibutyryl‐cyclic GMP induces peripheral antinociception via activation of ATP‐sensitive K + channels in the rat PGE 2 ‐induced hyperalgesic paw

2001; Wiley; Volume: 134; Issue: 1 Linguagem: Inglês

10.1038/sj.bjp.0704224

ISSN

1476-5381

Autores

Adriana C. Soares, Igor Dimitri Gama Duarte,

Tópico(s)

Botulinum Toxin and Related Neurological Disorders

Resumo

Using the rat paw pressure test, in which increased sensitivity is induced by intraplantar injection of prostaglandin E 2 , we studied the action of several K + channel blockers in order to determine what types of K + channels could be involved in the peripheral antinociception induced by dibutyrylguanosine 3 : 5′‐cyclic monophosphate (DbcGMP), a membrane permeable analogue of cyclic GMP. DbcGMP elicited a dose‐dependent (50, 75, 100 and 200 μg paw −1 ) peripheral antinociceptive effect. The effect of the 100 μg dose of DbcGMP was considered to be local since only a higher dose (300 μg paw −1 ) produced antinociception in the contralateral paw. The antinociceptive effect of DbcGMP (100 μg paw −1 ) was dose‐dependently antagonized by intraplantar administration of the sulphonylureas tolbutamide (20, 40 and 160 μg) and glibenclamide (40, 80 and 160 μg), selective blockers of ATP‐sensitive K + channels. Charybdotoxin (2 μg paw −1 ), a selective blocker of high conductance Ca 2+ ‐activated K + channels, and apamin (10 μg paw −1 ), a selective blocker of low conductance Ca 2+ ‐activated K + channels, did not modify the peripheral antinociception induced by DbcGMP. Tetraethylammonium (2 mg paw −1 ), 4‐aminopyridine (200 μg paw −1 ) and cesium (800 paw −1 ), non‐selective voltage‐gated potassium channel blockers, 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 DbcGMP induces peripheral antinociception, and that Ca 2+ ‐activated K + channels and voltage‐dependent K + channels appear not to be involved in the process. British Journal of Pharmacology (2001) 134 , 127–131; doi: 10.1038/sj.bjp.0704224

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