Role of pertussis toxin-sensitive G-protein, K+ channels, and voltage-gated Ca2+ channels in the antinociceptive effect of inosine

Autor: Murilo Luiz-Cerutti, Sérgio José Macedo-Júnior, Francisney Pinto do Nascimento, Adair R.S. Santos
Rok vydání: 2012
Předmět:
Zdroj: Purinergic Signalling. 9:51-58
ISSN: 1573-9546
1573-9538
Popis: 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 Ca(2+) channels, in the antinociception promoted by inosine in the formalin test. Mice were pretreated with pertussis toxin (2.5 μg/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 μg/site, i.t., a non-specific voltage-gated K(+) channel blockers), apamin (50 ng/site, i.t., a small conductance Ca(2+)-activated K(+) channel blocker), charybdotoxin (250 pg/site, i.t., a large-conductance Ca(2+)-activated K(+) channel blocker), glibenclamide (100 μg/site, i.t., an ATP-sensitive K(+) channel blocker) or CaCl(2) (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 μg/site, i.t.), TEA, 4-aminopyridine, charybdotoxin, glibenclamide, and CaCl(2), but not apamin. Further, all K(+) channel blockers and CaCl(2) 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 Ca(2+)-activated and ATP-sensitive K(+) channels or inactivation of voltage-gated Ca(2+) channels. Finally, small conductance Ca(2+)-activated K(+) channels are not involved in the antinociceptive effect of inosine.
Databáze: OpenAIRE
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