Zucker J
Department of Anesthesiology, University of Washington School of Medicine, Seattle 98195.
Anesth Analg. 1991 Jun;72(6):790-5. doi: 10.1213/00000539-199106000-00013.
The role of central nervous system cholinergic neuromechanisms during inhalation (isoflurane) anesthesia was evaluated by measuring the minimum alveolar concentration (MAC) in rats before and after selective modulation of cholinergic neurotransmission in the brain. Cholinergic neurotransmission was depressed by reducing synaptic levels of acetylcholine with intracerebroventricular (ICV) injection of the selective anticholinergic hemicholinium-3 and with ICV injection of the presynaptic inhibitory autoreceptor agonist oxotremorine. Hemicholinium-3 (20 micrograms) decreased MAC by 18% (P less than 0.001), and oxotremorine (20 micrograms) decreased MAC by 29% (P less than 0.001). Conversely, elevating synaptic levels of acetylcholine and facilitation of cholinergic neurotransmission by treatment with physostigmine significantly increased MAC. Antagonism of muscarinic receptors with ICV injection of atropine (30 micrograms) failed to alter MAC, but antagonism of nicotinic receptors with ICV injection of pancuronium significantly decreased MAC in a dose-dependent fashion. The results support the hypothesis that depressed cholinergic neurotransmission in the brain plays a role in the mediation of the anesthetized state. The consequences of depressed synaptic levels of acetylcholine during anesthesia may be mediated through a previously unidentified postsynaptic nicotinic neuromechanism.
通过测量大鼠在脑内胆碱能神经传递被选择性调节前后的最低肺泡浓度（MAC），评估了中枢神经系统胆碱能神经机制在吸入（异氟烷）麻醉过程中的作用。通过脑室内（ICV）注射选择性抗胆碱能药物半胱氨酸-3以及ICV注射突触前抑制性自身受体激动剂氧化震颤素，降低乙酰胆碱的突触水平，从而抑制胆碱能神经传递。半胱氨酸-3（20微克）使MAC降低了18%（P<0.001），氧化震颤素（20微克）使MAC降低了29%（P<0.001）。相反，用毒扁豆碱治疗提高乙酰胆碱的突触水平并促进胆碱能神经传递，可显著增加MAC。ICV注射阿托品（30微克）拮抗毒蕈碱受体未能改变MAC，但ICV注射泮库溴铵拮抗烟碱受体则以剂量依赖方式显著降低MAC。这些结果支持了这样的假说，即脑内胆碱能神经传递受抑制在麻醉状态的介导中起作用。麻醉期间乙酰胆碱突触水平降低的后果可能是通过一种先前未被识别的突触后烟碱神经机制介导的。
