Zhang Yi, Laster Michael J, Hara Koji, Harris R Adron, Eger Edmond I, Stabernack Caroline R, Sonner James M
Department of Anesthesia and Perioperative Care, University of California, San Francisco, 94143, USA.
Anesth Analg. 2003 Jan;96(1):97-101, table of contents. doi: 10.1097/00000539-200301000-00021.
Many inhaled anesthetics potentiate the effect of glycine on inhibitory strychnine-sensitive glycine receptors in vitro, supporting the view that this receptor could mediate the immobility produced by inhaled anesthetics during noxious stimulation (i.e., would underlie minimum alveolar anesthetic concentration [MAC]). There are quantitative differences between anesthetics in their capacity to potentiate glycine's effect in receptor expression systems: halothane (most potentiation), isoflurane (intermediate), and cyclopropane (minimal). If glycine receptors mediate MAC, then their blockade in the spinal cord should increase the MAC of halothane more than that of isoflurane and isoflurane MAC more than cyclopropane MAC; the increases in MAC should be proportional to the receptor potentiation produced in vitro. Rats with chronically implanted intrathecal catheters were anesthetized with halothane, isoflurane, or cyclopropane. During intrathecal infusion of artificial cerebrospinal fluid, MAC was determined. Then MAC was re-determined during an infusion of 3, 12, 24, or 48 (isoflurane only) micro g/min of strychnine (strychnine blocks glycine receptors) in artificial cerebrospinal fluid. Strychnine infusion increased MAC in proportion to the enhancement of glycine receptors found in vitro. The maximum effect was with an infusion of 12 micro g/min. For the combined results at 12 and 24 micro g/min of strychnine, the increase in MAC correlated with the extent of in vitro potentiation (r(2) = 0.82). These results support the hypothesis that glycine receptors mediate part of the immobilization produced by inhaled anesthetics.
In vitro, halothane potentiates glycine's effect on strychnine-sensitive glycine receptors more than isoflurane and isoflurane more than cyclopropane. The present in vivo work indicates that antagonism of the glycine receptor with strychnine increases minimum alveolar anesthetic concentration for halothane more than isoflurane and isoflurane more than cyclopropane. Such results support the notion that glycine receptors may mediate part of the immobility produced by inhaled anesthetics.
许多吸入麻醉药在体外可增强甘氨酸对士的宁敏感的甘氨酸受体的作用，这支持了一种观点，即该受体可能介导吸入麻醉药在有害刺激期间产生的制动作用（即，是最低肺泡麻醉浓度[MAC]的基础）。在受体表达系统中，不同麻醉药增强甘氨酸作用的能力存在定量差异：氟烷（增强作用最强）、异氟烷（中等）和环丙烷（最小）。如果甘氨酸受体介导MAC，那么在脊髓中阻断它们应该使氟烷的MAC增加幅度大于异氟烷，使异氟烷的MAC增加幅度大于环丙烷；MAC的增加应与体外产生的受体增强作用成比例。将长期植入鞘内导管的大鼠用氟烷、异氟烷或环丙烷麻醉。在鞘内输注人工脑脊液期间，测定MAC。然后在人工脑脊液中输注3、12、24或48（仅异氟烷为48）μg/min的士的宁（士的宁阻断甘氨酸受体）期间重新测定MAC。输注士的宁使MAC增加的幅度与体外发现的甘氨酸受体增强程度成比例。最大效应出现在输注速度为12μg/min时。对于士的宁输注速度为12和24μg/min时的综合结果，MAC的增加与体外增强程度相关（r(2)=0.82）。这些结果支持了甘氨酸受体介导吸入麻醉药产生的部分制动作用的假说。
在体外，氟烷比异氟烷更能增强甘氨酸对士的宁敏感的甘氨酸受体的作用，异氟烷比环丙烷更能增强。目前的体内研究表明，用士的宁拮抗甘氨酸受体使氟烷的最低肺泡麻醉浓度增加幅度大于异氟烷，异氟烷大于环丙烷。这些结果支持了甘氨酸受体可能介导吸入麻醉药产生的部分制动作用的观点。
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