Role of potassium channels in the antinociception induced by agonists of alpha(2)-adrenoceptors

1 The effect of the administration of pertussis toxin (PTX) as well as modu lators of different subtypes of K+ channels on the antinociception induced by clonidine and guanabenz was evaluated in the mouse hot plate test. 2 Pretreatment with pertussis toxin (0.25 mu g per mouse i.c.v.) 7 days bef ore the hot-plate test, prevented the antinociception induced by both cloni dine (0.08-0.2 mg kg(-1), s.c.) and guanabenz (0.1-0.5 mg kg(-1), s.c.). 3 The administration of the K-ATP channel openers minoxidil (10 mu g per mo use, i.c.v.), pinacidil (25 mu g per mouse, i.c.v.) and diazoxide (100 mg k g(-1), p.o.) potentiated the antinociception produced by clonidine and guan abenz whereas the K-ATP channel blocker gliquidone (6 mu g per mouse, i.c.v .) prevented the alpha(2) adrenoceptor agonist-induced analgesia. 4 Pretreatment with an antisense oligonucleotide (aODN) to mKv1.1, a voltag e-gated K+ channel, at the dose of 2.0 nmol per single i.c.v. injection, pr evented the antinociception induced by both clonidine and guanabenz in comp arison with degenerate oligonucleotide (dODN)-treated mice. 5 The administration of the Ca2+-gated K+ channel blocker apamin (0.5-2.0 n g per mouse, i.c.v.) never modified clonidine and guanabenz analgesia. 6 At the highest effective doses, none of the drugs used modified animals' gross behaviour nor impaired motor coordination, as revealed by the rota-ro d test. 7 The present data demonstrate that both K-ATP and mKv1.1 K+ channels repre sent an important step in the transduction mechanism underlying central ant inociception induced by activation of alpha(2) adrenoceptors.