Further analysis of the antinociceptive action caused byp-methoxyl-diphenyl diselenide in mice

Cristiano R. Jesse, Joao B.T. Rocha, Cristina W. Nogueira, Lucielli Savegnago, Cristiano R. Jesse, Joao B.T. Rocha, Cristina W. Nogueira, Lucielli Savegnago

Index: Pharmacol. Biochem. Behav. 91(4) , 573-80, (2009)

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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 N G-nitro- l-arginine ( l-NOARG, 75 mg/kg, i.p.) in the glutamate test. Ondansetron (0.5 mg/kg, i.p., a 5-HT 3 receptor antagonist) and SCH23390 (0.05 mg/kg, i.p.., a D 1 receptor antagonist) blocked the antinociceptive effect caused by (MeOPhSe) 2. Conversely, pindolol (1 mg/kg, i.p., a 5-HT 1A/ 1B receptor/β adrenoceptor antagonist), WAY 100635 (0.7 mg/kg, i.p., a selective 5-HT 1A receptor antagonist), ketanserin (0.3 mg/kg, i.p., a selective 5-HT 2A receptor antagonist), prazosin (0.15 mg/kg, i.p., an α 1-adrenoreceptor antagonist), yohimbine (1.0 mg/kg, i.p., an α 2-adrenoreceptor antagonist), sulpiride (5 mg/kg, i.p., a D 2 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-Arg 9-bradykinin (10 nmol/paw, a B 1 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-HT 3 and D 1 receptors. The antinociceptive effect is related to (MeOPhSe) 2 ability to interact with kinin B 1 and B 2 receptors and PKC pathway mediated mechanisms.