title: Involvement of ATP-sensitive K(+) channels in the peripheral antinociceptive effect induced by the alpha(2)-adrenoceptor agonist xylazine.
abstract: Xylazine is an alpha(2)-adrenergic agonist extensively used in veterinary medicine and animal experimentation for producing antinociception, sedation, and muscle relaxation. The nitric oxide (NO) / cGMP / ATP-sensitive K(+) (K(ATP)) channel pathway has been proposed as the action mechanism of peripheral antinociception of several groups of drugs, including opioids and nonsteroidal analgesics. Considering the lack of knowledge regarding the mechanisms involved in xylazine effects, the present study investigated the contribution of K(+) channels on peripheral antinociception induced by xylazine using the rat paw pressure test, in which hyperalgesia was induced by intraplantar injection of prostaglandin E(2). Xylazine administered into the right hind paw elicited a local antinociceptive effect, since only much higher doses produced a systemic effect in the contralateral paw. The peripheral antinociceptive effect induced by xylazine was antagonized by glibenclamide, a specific blocker of K(ATP) channels. In another experiment, tetraethylammonium, a voltage-dependent K(+)-channel blocker, and paxilline and dequalinium, which are selective blockers for the large- and small-conductance Ca(2+)-activated K(+) channels, respectively, were ineffective at blocking xylazine antinociception. These results provide evidence that the peripheral antinociceptive effect of xylazine probably results from K(ATP)-channel activation, while the voltage-dependent K(+) channels, small- and large-conductance Ca(2+)-activated K(+) channels, appear not to be involved in this mechanism.
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences (ICB), Federal University of Minas Gerais (UFMG), CEP 31.270.100, Belo Horizonte, MG, Brazil.
authors.forename: Thiago Roberto Lima
authors.initials: TR
authors.lastname: Romero
authors.forename: Igor Dimitri Gama
authors.initials: ID
authors.lastname: Duarte
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D015232:Dinoprostone; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy*; D007279:Injections, Subcutaneous; D054086:KATP Channels / Q000037:antagonists & inhibitors*; D008297:Male; D023421:Models, Animal; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014991:Xylazine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*
chemical_list: D000316:Adrenergic alpha-Agonists; D000700:Analgesics; D054086:KATP Channels; D026902:Potassium Channel Blockers; D014991:Xylazine; D015232:Dinoprostone