Article date: March 1999
By: Nicoletta Galeotti, Carla Ghelardini, Maria Cristina Vinci, Alessandro Bartolini, in Volume 126, Issue 5, pages 1214-1220
The effect of the administration of pertussis toxin (PTX) as well as modulators of different subtypes of K+ channels on the antinociception induced by clonidine and guanabenz was evaluated in the mouse hot plate test.
Pretreatment with pertussis toxin (0.25 μg 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−1, s.c.) and guanabenz (0.1–0.5 mg kg−1, s.c.).
The administration of the KATP channel openers minoxidil (10 μg per mouse, i.c.v.), pinacidil (25 μg per mouse, i.c.v.) and diazoxide (100 mg kg−1, p.o.) potentiated the antinociception produced by clonidine and guanabenz whereas the KATP channel blocker gliquidone (6 μg per mouse, i.c.v.) prevented the α2 adrenoceptor agonist‐induced analgesia.
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.
The administration of the Ca2+‐gated K+ channel blocker apamin (0.5–2.0 ng per mouse, i.c.v.) never modified clonidine and guanabenz analgesia.
At the highest effective doses, none of the drugs used modified animals' gross behaviour nor impaired motor coordination, as revealed by the rota‐rod test.
The present data demonstrate that both KATP and mKv1.1 K+ channels represent an important step in the transduction mechanism underlying central antinociception induced by activation of α2 adrenoceptors.
The effect of the administration of pertussis toxin (PTX) as well as modulators of different subtypes of K+ channels on the antinociception induced by clonidine and guanabenz was evaluated in the mouse hot plate test.
Pretreatment with pertussis toxin (0.25 μg 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−1, s.c.) and guanabenz (0.1–0.5 mg kg−1, s.c.).
The administration of the KATP channel openers minoxidil (10 μg per mouse, i.c.v.), pinacidil (25 μg per mouse, i.c.v.) and diazoxide (100 mg kg−1, p.o.) potentiated the antinociception produced by clonidine and guanabenz whereas the KATP channel blocker gliquidone (6 μg per mouse, i.c.v.) prevented the α2 adrenoceptor agonist‐induced analgesia.
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.
The administration of the Ca2+‐gated K+ channel blocker apamin (0.5–2.0 ng per mouse, i.c.v.) never modified clonidine and guanabenz analgesia.
At the highest effective doses, none of the drugs used modified animals' gross behaviour nor impaired motor coordination, as revealed by the rota‐rod test.
The present data demonstrate that both KATP and mKv1.1 K+ channels represent an important step in the transduction mechanism underlying central antinociception induced by activation of α2 adrenoceptors.
British Journal of Pharmacology (1999) 126, 1214–1220; doi:10.1038/sj.bjp.0702395
DOI: 10.1038/sj.bjp.0702395
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