期刊
PURINERGIC SIGNALLING
卷 9, 期 1, 页码 51-58出版社
SPRINGER
DOI: 10.1007/s11302-012-9327-2
关键词
Inosine; Pain; Potassium channels; Calcium channels; Pertussis toxin; Formalin test
资金
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
- Coordenacao de Aperfeicoamento de Pessoal de Nivel superior (CAPES)
Inosine is the first metabolite of adenosine. It exerts an antinociceptive effect by activating the adenosine A(1) and A(2A) receptors. We have previously demonstrated that inosine exhibits antinociceptive properties in acute and chronic mice models of nociception. The aim of this study was to investigate the involvement of pertussis toxin-sensitive G-protein-coupled receptors, as well as K+ and Ca2+ channels, in the antinociception promoted by inosine in the formalin test. Mice were pretreated with pertussis toxin (2.5 mu g/site, i.t., an inactivator of G(i/0) protein); after 7 days, they received inosine (10 mg/kg, i.p.) or morphine (2.5 mg/kg, s.c., used as positive control) immediately before the formalin test. Another group of animals received tetraethylammonium (TEA) or 4-aminopyridine (4-AP) (1 mu g/site, i.t., a non-specific voltage-gated K+ channel blockers), apamin (50 ng/site, i.t., a small conductance Ca2+-activated K+ channel blocker), charybdotoxin (250 pg/site, i.t., a large-conductance Ca2+-activated K+ channel blocker), glibenclamide (100 mu g/site, i.t., an ATP-sensitive K+ channel blocker) or CaCl2 (200 nmol/site, i.t.). Afterwards, the mice received inosine (10 mg/kg, i.p.), diclofenac (10 mg/kg, i.p., a positive control), or morphine (2.5 mg/kg, s.c., a positive control) immediately before the formalin test. The antinociceptive effect of inosine was reversed by the pre-administration of pertussis toxin (2.5 mu g/site, i.t.), TEA, 4-aminopyridine, charybdotoxin, glibenclamide, and CaCl2, but not apamin. Further, all K+ channel blockers and CaCl2 reversed the antinociception induced by diclofenac and morphine, respectively. Taken together, these data suggest that the antinociceptive effect of inosine is mediated, in part, by pertussis toxin-sensitive G-protein coupled receptors and the subsequent activation of voltage gated K+ channel, large conductance Ca2+-activated and ATP-sensitive K+ channels or inactivation of voltage-gated Ca2+ channels. Finally, small conductance Ca2+-activated K+ channels are not involved in the antinociceptive effect of inosine.
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