Article

Mechanisms involved in the antinociception induced by systemic administration of guanosine in mice

Department of Biochemistry, ICBS, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
British Journal of Pharmacology (Impact Factor: 4.84). 03/2010; 159(6):1247-63. DOI: 10.1111/j.1476-5381.2009.00597.x
Source: PubMed

ABSTRACT

It is well known that adenine-based purines exert multiple effects on pain transmission. However, less attention has been given to the potential effects of guanine-based purines on pain transmission. The aim of this study was to investigate the effects of intraperitoneal (i.p.) and oral (p.o.) administration of guanosine on mice pain models. Additionally, investigation into the mechanisms of action of guanosine, its potential toxicity and cerebrospinal fluid (CSF) purine levels were also assessed.
Mice received an i.p. or p.o. administration of vehicle (0.1 mM NaOH) or guanosine (up to 240 mg x kg(-1)) and were evaluated in several pain models.
Guanosine produced dose-dependent antinociceptive effects in the hot-plate, glutamate, capsaicin, formalin and acetic acid models, but it was ineffective in the tail-flick test. Additionally, guanosine produced a significant inhibition of biting behaviour induced by i.t. injection of glutamate, AMPA, kainate and trans-ACPD, but not against NMDA, substance P or capsaicin. The antinociceptive effects of guanosine were prevented by selective and non-selective adenosine receptor antagonists. Systemic administration of guanosine (120 mg x kg(-1)) induced an approximately sevenfold increase on CSF guanosine levels. Guanosine prevented the increase on spinal cord glutamate uptake induced by intraplantar capsaicin.
This study provides new evidence on the mechanism of action of the antinociceptive effects after systemic administration of guanosine. These effects seem to be related to the modulation of adenosine A(1) and A(2A) receptors and non-NMDA glutamate receptors.

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Available from: Elaine Elisabetsky, Oct 15, 2015
    • "An experimentally based hypothesis is that GUO caused an increase in extracellular ADO levels by competing with nucleoside transporter[19,20]. In fact, some of GUO's neuroprotective effects, but not all, are ADO receptor dependent181920212239]. Interestingly, radioactivity amounts were higher in brain structures following IP than IN[ 3 H]GUO solution administration . "
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    • "However, in relation to its antiepileptic/anticonvulsant effects, Guo (and GTP/GMP via degradation to Guo) [7] [126] might decrease excitability by the modulation of K + and Ca 2+ channel activity and may inhibit NMDA receptors via putative G i -protein-coupled Guo receptors similarly to A 1 receptors (Fig. 1). Although Guo may act independently of Ado and its receptors on astrocytic glutamate uptake and seizure activity [7] [34] [60] [121] [122], Guo also stimulates the release of Ado from astrocytes [9] [22] (Fig. 1) suggesting the involvement of the adenosinergic system in antiepileptic/anticonvulsant effect of Guo (e.g., via A 1 receptors), which is similar to the proposed mechanism of its antinociceptive effects [127] "
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