Wong Shirley M E, Sonner James M, Kendig Joan J
Department of Anesthesia, Stanford University School of Medicine, Stanford, CA 94305-5117, USA.
Anesth Analg. 2002 Jun;94(6):1495-9, table of contents. doi: 10.1097/00000539-200206000-00022.
Extensive studies on anesthetic mechanisms have focused on the nicotinic acetylcholine receptor, and to a lesser extent on the muscarinic receptor. We designed the present study to test the hypothesis that cholinergic receptors mediate some of the depressant actions of a volatile anesthetic in rat spinal cord. The cord was removed from 2- to 7-day-old rats and superfused in vitro; ventral root potentials were evoked by stimulating a lumbar dorsal root and recording from the corresponding ipsilateral ventral root. Both nicotine and muscarine depressed the nociceptive-related slow ventral root potential (sVRP). The nicotinic antagonists mecamylamine, methyllycaconitine, dihydro-beta-erythroidine, and the muscarinic antagonist atropine blocked the depressant effects of the respective agonists. Isoflurane 0.3 mini- mum alveolar anesthetic concentration depressed the sVRP area to approximately 40% of control. None of the antagonists changed the extent of isoflurane depression of the sVRP. The depressant actions of cholinergic agonists suggest that cholinergic receptors are important in spinal neurotransmission, but the lack of interaction between antagonists and isoflurane suggests that cholinergic receptors have little part in mediating the actions of this anesthetic in spinal cord. Because minimum alveolar anesthetic concentration is determined primarily in spinal cord, cholinergic receptors may be eliminated as molecular targets for this anesthetic end-point.
Neither nicotinic nor muscarinic acetylcholine receptor antagonists altered spinal cord actions of isoflurane, suggesting that these receptors have little role in isoflurane actions in spinal cord. Cholinergic receptors thus may be eliminated as molecular targets in determining the anesthetic end-point of immobility in response to a noxious stimulus (minimum alveolar anesthetic concentration).
关于麻醉机制的广泛研究主要集中在烟碱型乙酰胆碱受体上，对毒蕈碱型受体的研究较少。我们设计了本研究来检验胆碱能受体介导挥发性麻醉剂在大鼠脊髓中的一些抑制作用这一假说。从2至7日龄大鼠中取出脊髓并在体外进行灌流；通过刺激腰段背根并从相应的同侧腹根记录来诱发腹根电位。尼古丁和毒蕈碱均抑制与伤害感受相关的慢腹根电位（sVRP）。烟碱拮抗剂美加明、甲基lycaconitine、二氢-β-刺桐碱以及毒蕈碱拮抗剂阿托品阻断了各自激动剂的抑制作用。0.3最低肺泡麻醉浓度的异氟烷将sVRP面积抑制至对照的约40%。没有一种拮抗剂改变异氟烷对sVRP的抑制程度。胆碱能激动剂的抑制作用表明胆碱能受体在脊髓神经传递中很重要，但拮抗剂与异氟烷之间缺乏相互作用表明胆碱能受体在介导这种麻醉剂在脊髓中的作用方面作用很小。由于最低肺泡麻醉浓度主要在脊髓中确定，胆碱能受体可能不再作为这种麻醉终点的分子靶点。
烟碱型和毒蕈碱型乙酰胆碱受体拮抗剂均未改变异氟烷在脊髓中的作用，表明这些受体在异氟烷在脊髓中的作用中作用很小。因此，在确定对有害刺激（最低肺泡麻醉浓度）的麻醉终点即不动性时，胆碱能受体可能不再作为分子靶点。
