Role of potassium channels in the antinociception induced by agonists of α₂‐adrenoceptors

Abstract

1 The e ect of the administration of pertussis toxin (PTX) as well as modulators of di erent 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 mg per mouse i.c.v.) 7 days before the hot-plate test, prevented the antinociception induced by both clonidine (0.08 ± 0.2 mg kg 71 , s.c.) and guanabenz (0.1 ± 0.5 mg kg 71 , s.c.). 3 The administration of the K ATP channel openers minoxidil (10 mg per mouse, i.c.v.), pinacidil (25 mg per mouse, i.c.v.) and diazoxide (100 mg kg 71 , p.o.) potentiated the antinociception produced by clonidine and guanabenz whereas the K ATP channel blocker gliquidone (6 mg per mouse, i.c.v.) prevented the a 2 adrenoceptor agonist-induced analgesia. 4 Pretreatment with an antisense oligonucleotide (aODN) to mKv1.1, a voltage-gated K + channel, at the dose of 2.0 nmol per single i.c.v. injection, prevented the antinociception induced by both clonidine and guanabenz in comparison with degenerate oligonucleotide (dODN)-treated mice. 5 The administration of the Ca 2+ -gated K + channel blocker apamin (0.5 ± 2.0 ng per mouse, i.c.v.) never modi®ed clonidine and guanabenz analgesia. 6 At the highest e ective doses, none of the drugs used modi®ed animals' gross behaviour nor impaired motor coordination, as revealed by the rota-rod test.7 The present data demonstrate that both K ATP and mKv1.1 K + channels represent an important step in the transduction mechanism underlying central antinociception induced by activation of a 2 adrenoceptors.

Involvement of potassium channels in amitriptyline and clomipramine analgesia

“…Furthermore, the α subunits involved in the modulation of K ATP channel function have been identified as belonging to the α i and α o subtypes (Edwards and Weston, 1993). From this evidence, we can suppose that K ATP channels are involved in the analgesia induced by amitriptyline and clomipramine as an intracellular effector underlying the activation of a G i (Ocaña et al, 1990;Wild et al, 1991;Ocaña and Baeyens, 1994;Ghelardini et al, 1998;Galeotti et al, 1999). Taken together, these data indicate that the opening of K ATP channels is a signal transduction mechanism common to analgesic drugs interacting with G i proteins.…”

Involvement of Potassium Channels in Spinal Antinociceptions Induced by Fentanyl, Clonidine and Bethanechol in Rats

“…The antinociception induced by clonidine was partially antagonized by both glibenclamide and charybdotoxin. The K + ATP channel blockers glibenclamide and gliquidone antagonize the antinociception induced by a 2 adrenergic agonists such as clonidine, tizanidine, guanabentz and dexmedetomidine (18,26,27,31). These reports showed that both K + ATP channels and Ca…”

“…Transmission of a noxious stimulus to the postsynaptic membrane is consequently suppressed. The K + ATP channel openers, including cromakalim, minoxidil, pinacidil, diazoxide, nicorandil and levcromakalim, enhance the antinociceptive effects induced by a2 adrenergic agonists such as clonidine, guanabentz and dexmedetomidine (18,27,31). Similar to the interaction mechanisms of opioids and K + channel openers, the interaction of clonidine and K + channel is probably not direct, but rather may occur via simultaneous activation of a common second messenger within individual neurons.…”

“…-activated K + channels than those on K + ATP channels in antinociception in the spinal cord (17,31). Ca 2+ -activated K + channels are structurally similar to voltage-gated K + channels and the open probability is also governed by intracellular Ca 2+ concentration.…”

Involvement of ATP-Sensitive K+ Channels in the Peripheral Antinociceptive Effect Induced by the α2-Adrenoceptor Agonist Xylazine

“…Ocaña and Baeyens (22) reported that K ATP channels were involved in the central antinociceptive mechanism of the α 2 -adrenergic agonist clonidine in the tail-flick test since glibenclamide antagonized this effect; and in the same work, voltage-dependent K + channels participation was discarded since 4-aminopyridine and tetraethylammonium were unable to reverse the effect of clonidine. Besides clonidine, the antinociception of several other α 2 -adrenergic agonists, including guanabenz, tizanidine, and dexmedetomidine, were antagonized by the sulphonylureas tolbutamide and glibenclamide, reaffirming the importance of K ATP -channel activation regarding the antinociceptive action of α 2 -adrenergic agonists (23).…”