Monroe P J, Smith D L, Kirk H R, Smith D J
Department of Anesthesiology, Robert C. Byrd Health Sciences Center of West Virginia University, Morgantown, USA.
J Pharmacol Exp Ther. 1995 Jun;273(3):1057-62.
The intrathecal administration of clonidine to rats results in profound antinociception which is thought to be mediated through an interaction of the agonist with spinal alpha-2 adrenergic receptors. However, clonidine has been shown to also interact with nonadrenergic imidazoline receptors. Consequently, this study was undertaken to determine if nonadrenergic imidazoline receptors are present in the rat spinal cord, and the extent to which they are involved in the antinociceptive action of spinally administered clonidine. By using the tail-flick test, the antinociceptive action of spinally administered clonidine was found to be blocked completely by the intrathecal administration of the imidazoline idazoxan. Similarly, yohimbine (a nonimidazoline alpha-2 adrenergic antagonist) also blocked completely the antinociceptive action of clonidine. Results of radioligand binding studies demonstrated that norepinephrine did not interact with approximately 20% of all specific spinal sites labeled by 4 nM [3H]clonidine, indicating the presence of nonadrenergic spinal sites. Affinity data obtained from competition binding assays demonstrated that the spinal nonadrenergic sites labeled by [3H]clonidine possess little affinity for yohimbine. Therefore, nonadrenergic imidazoline receptors are not involved in the antinociceptive action of spinally administered clonidine.
向大鼠鞘内注射可乐定可产生显著的镇痛作用，这被认为是通过激动剂与脊髓α-2肾上腺素能受体相互作用介导的。然而，已证明可乐定也能与非肾上腺素能咪唑啉受体相互作用。因此，开展本研究以确定大鼠脊髓中是否存在非肾上腺素能咪唑啉受体，以及它们在鞘内注射可乐定的镇痛作用中所涉及的程度。通过使用甩尾试验，发现鞘内注射咪唑啉类药物伊达唑胺可完全阻断鞘内注射可乐定的镇痛作用。同样，育亨宾（一种非咪唑啉类α-2肾上腺素能拮抗剂）也完全阻断了可乐定的镇痛作用。放射性配体结合研究结果表明，去甲肾上腺素不与4 nM [3H]可乐定标记的所有特异性脊髓位点中的约20%相互作用，表明存在非肾上腺素能脊髓位点。从竞争结合试验获得的亲和力数据表明，[3H]可乐定标记的脊髓非肾上腺素能位点对育亨宾的亲和力很小。因此，非肾上腺素能咪唑啉受体不参与鞘内注射可乐定的镇痛作用。
