The effects of the alpha2-adrenergic receptor agonists clonidine and rilmenidine, and antagonists yohimbine and efaroxan, on the spinal cholinergic receptor system in the rat

Research output: Contribution to journalJournal articleResearchpeer-review

Klas S P Abelson, A Urban Höglund

Cholinergic agonists produce spinal antinociception via mechanisms involving an increased release of intraspinal acetylcholine. The cholinergic receptor system interacts with several other receptor types, such as alpha2-adrenergic receptors. To fully understand these interactions, the effects of various receptor ligands on the cholinergic system must be investigated in detail. This study was initiated to investigate the effects of the alpha2-adrenergic receptor agonists clonidine and rilmenidine and the alpha2-adrenergic receptor antagonists yohimbine and efaroxan on spinal cholinergic receptors in the rat. Spinal microdialysis was used to measure in vivo changes of acetylcholine after administration of the ligands, with or without nicotinic receptor blockade. In addition, in vitro binding properties of the ligands on muscarinic and nicotinic receptors were investigated. It was found that clonidine and rilmenidine increased, while yohimbine decreased spinal acetylcholine release. Efaroxan affected acetylcholine release differently depending on concentration. Nicotinic receptor blockade attenuated the effect of all ligands. All ligands showed poor binding affinity for muscarinic receptors. On the other hand, all ligands possessed affinity for nicotinic receptors. Clonidine and yohimbine binding was best fit to a one site binding curve and rilmenidine and efaroxan to a two site binding curve. The present study demonstrates that the tested alpha2-adrenergic receptor ligands affect intraspinal acetylcholine release in the rat evoked by nicotinic receptor mechanisms in vivo, and that they possess binding affinity to nicotinic receptors in vitro. The binding of alpha2-adrenergic receptor ligands to nicotinic receptors might affect the intraspinal release of acetylcholine.
Original languageEnglish
JournalBasic & Clinical Pharmacology & Toxicology
Issue number4
Pages (from-to)153-60
Number of pages8
Publication statusPublished - Apr 2004

    Research areas

  • Acetylcholine, Adrenergic alpha-2 Receptor Agonists, Adrenergic alpha-2 Receptor Antagonists, Animals, Benzofurans, Binding, Competitive, Clonidine, Dose-Response Relationship, Drug, Imidazoles, Injections, Spinal, Ligands, Male, Microdialysis, Oxazoles, Rats, Rats, Sprague-Dawley, Receptors, Adrenergic, alpha-2, Receptors, Cholinergic, Spinal Cord, Time Factors, Yohimbine

ID: 48010516