Role of K+-channels in homotaurine-induced analgesia

In previous articles, antinociceptive activity for homotaurine has been dem onstrated to be mediated by opioid, GABAergic and cholinergic mechanisms. G ABAB-agonists affect K+-channels and it is known that K+-channels modulate specific activation of opioid receptors. In this study, we examined the inv olvement of K+-channels in the antinociceptive activity of homotaurine (22- 445 mg/kg). Antinociceptive response was obtained after icv pretreatment wi th the channel specific blockers 4-aminopyridine (voltage-dependent channel s), tetraethylammonium (Ca++ and voltage-dependent) and gliquidone (ATP-dep endent). The nociceptive tests performed were acetic acid induced abdominal constriction (mice) and tail flick (rats) tests. Acetic acid responses to homotaurine were inhibited by tetraethylammonium (5 mug) and gliquidone (16 mug). Tail flick response to homotaurine was inhibited by tetraethylammoni um (50 mug), gliquidone (40 and 80 mug) and 4-aminopyridine (25 and 250 ng) . These results suggest an involvement of the three types of K+-channels in antinociception by homotaurine, depending on specific homotaurine and bloc ker doses. At a spinal level, they appear to be involved together with GABA (B) and opioid mechanisms. Peripherally, only tetraethylammonium channels w ould be substantially activated during homotaurine antinociceptive effect.