Abelson Klas S P, Höglund A Urban
Department of Neuroscience, Division of Comparative Medicine, Biomedical Centre, Uppsala University, Uppsala, Sweden.
Basic Clin Pharmacol Toxicol. 2004 Apr;94(4):153-60. doi: 10.1111/j.1742-7843.2004.pto940401.x.
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.
胆碱能激动剂通过增加脊髓内乙酰胆碱的释放机制产生脊髓镇痛作用。胆碱能受体系统与其他几种受体类型相互作用，如α2-肾上腺素能受体。为了充分理解这些相互作用，必须详细研究各种受体配体对胆碱能系统的影响。本研究旨在探讨α2-肾上腺素能受体激动剂可乐定和利美尼定以及α2-肾上腺素能受体拮抗剂育亨宾和依酚氯铵对大鼠脊髓胆碱能受体的影响。采用脊髓微透析法测量给予配体后体内乙酰胆碱的变化，同时或不进行烟碱受体阻断。此外，还研究了配体对毒蕈碱和烟碱受体的体外结合特性。结果发现，可乐定和利美尼定增加脊髓乙酰胆碱释放，而育亨宾则降低其释放。依酚氯铵根据浓度不同对乙酰胆碱释放有不同影响。烟碱受体阻断减弱了所有配体的作用。所有配体对毒蕈碱受体的结合亲和力都很差。另一方面，所有配体对烟碱受体都有亲和力。可乐定和育亨宾的结合最符合单点结合曲线，利美尼定和依酚氯铵符合两点结合曲线。本研究表明，所测试的α2-肾上腺素能受体配体在体内通过烟碱受体机制影响大鼠脊髓内乙酰胆碱的释放，并且它们在体外对烟碱受体具有结合亲和力。α2-肾上腺素能受体配体与烟碱受体的结合可能会影响脊髓内乙酰胆碱的释放。
