Involvement of ATP-sensitive K(+) channels in the peripheral antinociceptive effect induced by dipyrone.
We evaluated the effect of several K(+) channel blockers on the peripheral antinociception induced by dipyrone using the rat paw pressure test, in which sensitivity is increased by intraplantar injection (2 micro g) of prostaglandin E(2). Dipyrone administered locally into the right hindpaw (50, 100 and 200 micro g) elicited a dose-dependent antinociceptive effect which was demonstrated to be local, since only higher doses produced an effect when injected in the contralateral paw. The specific blockers of ATP-sensitive K(+) channels glibenclamide (40, 80 and 160 micro g/paw) and tolbutamide (80, 160 and 320 micro g/paw) antagonized the peripheral antinociception induced by dipyrone (200 micro g/paw). Charybdotoxin (2 micro g/ paw), a blocker of large conductance Ca(2+)-activated K(+) channels, and dequalinium (50 micro g/paw), a selective blocker of small conductance Ca(2+)-activated K(+) channels, did not modify the effect of dipyrone. This effect was also unaffected neither by intraplantar administration of non-specific voltage-dependent K(+) channel blockers tetraethylammonium (1700 micro g) and 4-aminopyridine (100 micro g) nor cesium (500 micro g), a non-specific K(+) channel blocker. These results suggest that the peripheral antinociceptive effect of dipyrone may result from activation of ATP-sensitive K(+) channels, while other K(+) channels appear not to be involved in the process.
Department of Pharmacology, Institute of Biological Sciences, UFMG, Av. Antônio Carlos, 6627-Campus da Pampulha, Belo Horizonte, MG, CEP 31270-100, Brazil.
Daniela
D
Alves
Igor
I
Duarte
D000255:Adenosine Triphosphate / Q000502:physiology*; D000698:Analgesia; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004177:Dipyrone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D005905:Glyburide / Q000494:pharmacology; D008297:Male; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D014044:Tolbutamide / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D004177:Dipyrone; D000255:Adenosine Triphosphate; D014044:Tolbutamide; D005905:Glyburide