Role of K+ -channels in homotaurine-induced analgesia

In previous articles, antinociceptive activity for homotaurine has been demonstrated to be mediated by opioid, GABAergic and cholinergic mechanisms. GABAB-agonists affect K+-channels and it is known that K+-channels modulate specific activation of opioid receptors. In this study, we examined the involvement of K+-channels in the antinociceptive activity of homotaurine (22-445 mg/kg). Antinociceptive response was obtained after icv pretreatment with the channel specific blockers 4-aminopyridine (voltage-dependent channels), tetraethylammonium (Ca++ and voltage-dependent) and gliquidone (ATP-dependent). 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 microg) and gliquidone (16 microg). Tail flick response to homotaurine was inhibited by tetraethylammonium (50 microg), gliquidone (40 and 80 microg) 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 blocker doses. At a spinal level, they appear to be involved together with GABAB and opioid mechanisms. Peripherally, only tetraethylammonium channels would be substantially activated during homotaurine antinociceptive effect.