Delta-opioid receptor agonist SNC80 induces peripheral antinociception via activation of ATP-sensitive K+ channels.
We investigated the effect of several K+ channel blockers on the antinociception induced by delta-opioid receptor agonist SNC80 using the paw pressure test, in which pain sensitivity is increased by an intraplantar injection (2 microg) of prostaglandin E2 (PGE2). Administration of SNC80 (20, 40 and 80 microg/paw) caused a decrease in the hyperalgesia induced by PGE2, in a dose-dependent manner. The possibility of higher dose of SNC80 (80 microg) causing a central or systemic effect was excluded since administration of the drug into the contralateral paw did not elicit antinociception in the right paw. Specific blockers of ATP-sensitive K+ channels, glibenclamide (20, 40 and 80 microg/paw) and tolbutamide (40, 80 and 160 microg/paw), antagonized the peripheral antinociception induced by SNC80 (80 microg). On the other hand, charybdotoxin (2 microg/paw), a large-conductance blocker of Ca(2+)-activated K+ channels, and dequalinium (50 microg/paw), a small conductance selective blocker of Ca(2+)-activated K+ channels, did not modify the effect of SNC80. This effect also remained unaffected by intraplantar administration of the voltage-dependent K+ channel blockers tetraethylammonium (30 microg/paw) and 4-aminopyridine (10 microg/paw), and of a non-specific K+ channel blocker, cesium (500 microg/paw). This study provides evidence that the peripheral antinociceptive effect of SNC80 result from the activation of ATP-sensitive K+ channels, and the other K+ channels are not involved.
Pacheco
Daniela F
DF
Department of Pharmacology, Institute of Biological Sciences, ICB-UFMG, Av. Antônio Carlos, 6627-Campus da Pampulha, CEP 31.270.100, Belo Horizonte, MG, Brazil.
Duarte
Igor D G
ID
D000255:Adenosine Triphosphate / Q000502:physiology*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001549:Benzamides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D008297:Male; D010879:Piperazines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000819:agonists*
D000700:Analgesics; D001549:Benzamides; D002121:Calcium Channel Blockers; D010879:Piperazines; D015221:Potassium Channels; D017465:Receptors, Opioid, delta; C088464:4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide; D000255:Adenosine Triphosphate