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

Nicoletta Galeotti, Carla Ghelardini, Maria Cristina Vinci, Alessandro Bartolini

Research output: Contribution to journalArticle

Abstract

1. 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. 2. 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.). 3. The administration of the K(ATP) 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 K(ATP) channel blocker gliquidone (6 μg per mouse, i.c.v.) prevented the α2 adrenoceptor agonist-induced analgesia. 4. Pretreatment with an antisense oligonucleotide (aODN) to mKvl.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 Ca2+-gated K+ channel blocker apamin (0.5-2.0 ng 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-rod test. 7. The present data demonstrate that both K(ATP) and mKvl.1 K+ channels represent an important step in the transduction mechanism underlying central antinociception induced by activation of α2 adrenoceptors.

Original languageEnglish
Pages (from-to)1214-1220
Number of pages7
JournalBritish Journal of Pharmacology
Volume126
Issue number5
Publication statusPublished - 1999

Keywords

  • Antinociception
  • Apamin
  • Clonidine
  • Diazoxide
  • Gliquidone
  • Guanabenz
  • K channel
  • Kvl.1
  • Minoxidil
  • Pinacidil

ASJC Scopus subject areas

  • Pharmacology

Fingerprint Dive into the research topics of 'Role of potassium channels in the antinociception induced by agonists of α<sub>2</sub>-adrenoceptors'. Together they form a unique fingerprint.

  • Cite this