title: Small conductance calcium-activated K+ channels, SkCa, but not voltage-gated K+ (Kv) channels, are implicated in the antinociception induced by CGS21680, a A2A adenosine receptor agonist.
abstract: It has been shown that A2A adenosine receptors are implicated in pain modulation. The precise mechanism by which activation of A2A receptors produces analgesic effects, however, remains unclear. The aim of this study was to investigate the possible involvement of apamin-sensitive calcium-activated potassium channels (SKCa) and voltage-gated potassium (Kv) channels in A2A receptor activation-induced analgesic effects. Using mice, we evaluated the influence of apamin, a non specific blocker of SKCa channels, Lei-Dab7 (an analog of scorpion Leiurotoxin), a selective blocker of SKCa2 channels, and kaliotoxin (KTX) a Kv channel blocker, on the CGS 21680 (A2A adenosine receptor agonist)-induced increases in hot plate and tail pinch latencies. All drugs were injected in mice via the intracerebroventricular route. We found that apamin and Lei-Dab7, but not KTX, reduced antinociception produced by CGS21680 on the hot plate and tail pinch tests in a dose dependent manner. Lei-Dab 7 was more potent than apamin in this regard. We conclude that SKCa but not Kv channels are implicated in CGS 21680-induced antinociception.
authors.affiliation: UMR FRE CNRS 2738 Ingénierie des Protéines, Faculté de Médecine Nord, Bd P, Dramard 13015 Marseille, France.
authors.forename: I
authors.initials: I
authors.lastname: Regaya
authors.forename: T
authors.initials: T
authors.lastname: Pham
authors.forename: N
authors.initials: N
authors.lastname: Andreotti
authors.forename: N
authors.initials: N
authors.lastname: Sauze
authors.forename: L
authors.initials: L
authors.lastname: Carrega
authors.forename: M F
authors.initials: MF
authors.lastname: Martin-Eauclaire
authors.forename: B
authors.initials: B
authors.lastname: Jouirou
authors.forename: J C
authors.initials: JC
authors.lastname: Peragut
authors.forename: H
authors.initials: H
authors.lastname: Vacher
authors.forename: H
authors.initials: H
authors.lastname: Rochat
authors.forename: C
authors.initials: C
authors.lastname: Devaux
authors.forename: J M
authors.initials: JM
authors.lastname: Sabatier
authors.forename: R
authors.initials: R
authors.lastname: Guieu
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D058917:Adenosine A2 Receptor Antagonists; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D004359:Drug Therapy, Combination; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010146:Pain / Q000517:prevention & control*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D010627:Phenethylamines / Q000008:administration & dosage / Q000494:pharmacology*; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors*; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors*; D012604:Scorpion Venoms / Q000494:pharmacology
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D000700:Analgesics; D010627:Phenethylamines; D024681:Potassium Channels, Calcium-Activated; D024642:Potassium Channels, Voltage-Gated; D012604:Scorpion Venoms; C442227:diaminobutanoyl(7)-leiurotoxin I; C072276:kaliotoxin; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D001030:Apamin; D000241:Adenosine