Honda Kenji, Ando Suguru, Koga Kohei, Takano Yukio
Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan.
Neurosci Lett. 2004 Nov 23;371(2-3):235-8. doi: 10.1016/j.neulet.2004.09.003.
The present study was undertaken to clarify how spinal muscarinic receptors can be involved in the antinociceptive effects induced by morphine in thermal stimulation. The morphine-induced antinociceptive effects (26.6 micromol/kg, s.c.) was inhibited by an intrathecal (i.t.) injection of the muscarinic antagonist (M) atropine and the M(1)/M(4) antagonist pirenzepine in a dose-dependent manner. In contrast, the M(2) antagonist methoctramine and the M(3) antagonist 4-DAMP did not inhibit the morphine-induced antinociceptive effects. Injection (i.t.) of the putative M(1) agonist McN-A-343 resulted in dose-dependent antinociceptive effects in thermal stimuli. In addition, antinociceptive effects induced by the i.t. injection of morphine were not inhibited by the M(1)/M(4) antagonist pirenzepine, although pirenzepine did inhibit the intracerebroventricular (i.c.v.) injection of morphine-induced antinociceptive effects. These results suggest that the morphine-induced antinociceptive effects in thermal stimuli are regulated by the M(1) or M(4) receptor in the spinal cord.
本研究旨在阐明脊髓毒蕈碱受体如何参与吗啡在热刺激中诱导的抗伤害感受作用。鞘内注射毒蕈碱拮抗剂阿托品和M(1)/M(4)拮抗剂哌仑西平，可剂量依赖性地抑制吗啡诱导的抗伤害感受作用（26.6微摩尔/千克，皮下注射）。相比之下，M(2)拮抗剂甲溴东莨菪碱和M(3)拮抗剂4-DAMP并不抑制吗啡诱导的抗伤害感受作用。鞘内注射假定的M(1)激动剂 McN-A-343可在热刺激中产生剂量依赖性的抗伤害感受作用。此外，尽管哌仑西平确实抑制脑室内注射吗啡诱导的抗伤害感受作用，但鞘内注射吗啡诱导的抗伤害感受作用并不受M(1)/M(4)拮抗剂哌仑西平的抑制。这些结果表明，吗啡在热刺激中诱导的抗伤害感受作用受脊髓中的M(1)或M(4)受体调节。
