It is well known that adenine-based purines exert multiple effects on pain transmission. Less attention has been given, however, to the antinociceptive effects of guanine-based purines. The aim of this study was to investigate the effects of intraperitoneal administration of guanosine on a rat model of peripheral mononeuropathy. Additionally, investigation of the mechanism of action of guanosine, its general toxicity and measurements of central nervous system purine levels were performed. Rats received an intraperitoneal administration of vehicle (0.1 mM NaOH) or guanosine (up to 120 mg.kg(-1)) in an acute or chronic regimen. Guanosine significantly reduced thermal hyperalgesia on the ipsilateral side of the sciatic nerve ligation. Additionally, guanosine prevented locomotor deficits and body weight loss induced by the mononeuropathy. Acute systemic administration of guanosine caused an approximately 11-fold increase on central nervous system guanosine levels, but this effect was not observed after chronic treatment. Chronic guanosine administration prevented the increase on cortical glutamate uptake but not the decrease in spinal cord glutamate uptake induced by the mononeuropathy. No significant general toxicity was observed after chronic exposure to guanosine. This study provides new evidence on the mechanism of action of guanine-based purines, with guanosine presenting antinociceptive effects against a chronic pain model. PERSPECTIVE: This study provides a new role for guanosine: chronic pain modulation. Guanosine presents as a new target for future drug development and might be useful for treatment of neuropathic pain.
"In relation to the LPS-evoked absence epileptic activity changes, our results suggest a crosstalk between LPS-induced TLR4/IL-1R/proinflammatory cytokine system, glutamatergic system , GABAergic system and adenosinergic system, in which processes non-Ado nucleosides may have modulatory functions. Guo and Urd have very low toxicity (Schmidt et al., 2010; Zhao et al., 2008). Thus, these endogenous molecules may be useful in the treatment of neuroinflammatory/inflammation-modulated CNS diseases such as epilepsy. "
[Show abstract][Hide abstract] ABSTRACT: We showed previously that the number of spike-wave discharges (SWDs) was increased after intraperitoneal (i.p.) injection of lipopolysaccharide (LPS), inosine (Ino) and muscimol alone whereas i.p. guanosine (Guo), uridine (Urd), bicuculline, theophylline and (+)-5-methyl-10,11-dihydro-5H-dibenzo (a,d) cyclohepten-5,10-imine maleate (MK-801) alone decreased the SWD number in Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. These drugs may exert their effects on absence epileptic activity mainly via proinflammatory cytokines-evoked increase in cortical excitability (such as LPS), GABAergic system (LPS, Ino, Urd, muscimol and bicuculline), glutamatergic system (LPS, Guo and MK-801) and adenosinergic system (LPS, Ino, Guo, Urd and theophylline). Both GABAergic system and glutamatergic system are involved in the pathomechanism of absence epilepsy, the LPS-evoked increase in absence epileptic activity and the pro- or antiepileptic effects of non-adenosine (non-Ado) nucleosides Ino, Guo and Urd. Moreover, Ino, Guo and Urd have modulatory effects on inflammatory processes. Thus, we investigated whether Ino, Guo and Urd have also modulatory influence on LPS-evoked increase in SWD number using two different concentrations of each nucleoside in WAG/Rij rats. We demonstrated that Ino dose-dependently aggravated whereas Guo and Urd attenuated the LPS-evoked increase in SWD number. Our results suggest that different nucleosides have diverse effects on LPS-induced changes in absence epileptic activity.
Brain research bulletin 09/2015; DOI:10.1016/j.brainresbull.2015.09.003 · 2.72 Impact Factor
"Guo and Urd. Our results imply that Guo, Urd and their analogs may be useful, effective and safe antiepileptic drugs (Lara et al., 2001; Kimura et al., 2001b; Kova´cs and Dobolyi, 2013; Kova´cs et al., 2014) in the treatment of human absence epilepsy because Guo and Urd are well tolerated drugs with only minor toxic potential as demonstrated previously (Lara et al., 2001; Vinadeét al., 2003; Zhao et al., 2008; Schmidt et al., 2010). "
[Show abstract][Hide abstract] ABSTRACT: Guanine-based purines have been traditionally studied as modulators of intracellular processes, mainly G-protein activity. However, more recently, several studies have shown that they exert a variety of extracellular effects not related to G-proteins, including trophic effects on neural cells, modulation of glutamatergic activity, behavioral effects and anticonvulsant activity. In this article, the putative effects of the guanine-based purines against seizures and neurotox-icity are reviewed. Current evidence suggests that guanine-based purines, especially guanosine, seem to be endogenous anticonvulsant substances, perhaps in a similar way to the adenine-based purines. Although studies addressing the mecha-nism of action of guanine-based purines are still lacking, their anticonvulsant activity is probably related to the modula-tion of several glutamatergic parameters, especially the astrocytic glutamate uptake. These findings point to the guanine-based purines as potential new targets for the development of novel drugs for neuroprotection and management of epi-lepsy.
The Open Neuroscience Journal 01/2010; 4(1). DOI:10.2174/1874082001004010102
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.