Further analysis of the antinociceptive action caused by p-methoxyl-diphenyl diselenide in mice |
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Authors: | Jesse Cristiano R Rocha Joao B T Nogueira Cristina W Savegnago Lucielli |
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Affiliation: | a Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, RS, Brazil b Universidade Federal do Pampa (UNIPAMPA), Campus Uruguaiana, BR 472 KM 7, CEP 97500-970, Caixa Postal 118, Uruguaiana, RS, Brazil |
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Abstract: | The objective of this study was to extend our previous findings by investigating in greater detail the mechanisms that might be involved in the antinociceptive action of p-methoxyl-diphenyl diselenide, (MeOPhSe)2, in mice. The pretreatment with nitric oxide precursor, l-arginine (600 mg/kg, intraperitoneal, i.p.), reversed antinociception caused by (MeOPhSe)2 (10 mg/kg, p.o.) or NG-nitro-l-arginine (l-NOARG, 75 mg/kg, i.p.) in the glutamate test. Ondansetron (0.5 mg/kg, i.p., a 5-HT3 receptor antagonist) and SCH23390 (0.05 mg/kg, i.p.., a D1 receptor antagonist) blocked the antinociceptive effect caused by (MeOPhSe)2. Conversely, pindolol (1 mg/kg, i.p., a 5-HT1A/1B receptor/β adrenoceptor antagonist), WAY 100635 (0.7 mg/kg, i.p., a selective 5-HT1A receptor antagonist), ketanserin (0.3 mg/kg, i.p., a selective 5-HT2A receptor antagonist), prazosin (0.15 mg/kg, i.p., an α1-adrenoreceptor antagonist), yohimbine (1.0 mg/kg, i.p., an α2-adrenoreceptor antagonist), sulpiride (5 mg/kg, i.p., a D2 receptor antagonist), naloxone (1 mg/kg, i.p., a non-selective opioid receptor antagonist) and caffeine (3 mg/kg, i.p., a non-selective adenosine receptor antagonist) did not change the antinociceptive effect of (MeOPhSe)2. (MeOPhSe)2 significantly inhibited nociception induced by intraplantar (i.pl.) injection of bradykinin (10 nmol/paw) and Des-Arg9-bradykinin (10 nmol/paw, a B1 receptor agonist). (MeOPhSe)2 significantly inhibited phorbol myristate acetate (PMA, 0.03 μg/paw, a protein kinase C (PKC) activator)-induced licking response. These results indicate that (MeOPhSe)2 produced antinociception in mice through mechanisms that involve an interaction with nitrergic system, 5-HT3 and D1 receptors. The antinociceptive effect is related to (MeOPhSe)2 ability to interact with kinin B1 and B2 receptors and PKC pathway mediated mechanisms. |
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Keywords: | Selenium Organoselenium Antinociceptive Mechanisms of action Mice |
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