Kikuchi T, Wang Y, Sato K, Okumura F
Department of Anaesthesiology, Yokohama City University School of Medicine, Japan.
Br J Anaesth. 1998 May;80(5):644-8. doi: 10.1093/bja/80.5.644.
Using in vivo microdialysis, we have investigated the effects of propofol on acetylcholine (ACh) release from various regions of the rat brain. Propofol 25 and 50 mg kg-1 i.p. decreased basal ACh release from the frontal cortex by 70% and 85%, respectively. Propofol 25 and 50 mg kg-1 i.p. decreased basal ACh release from the hippocampus by 47% and 72%, respectively. However, in rat striatum, propofol 25 mg kg-1 i.p. did not affect basal ACh release and 50 mg kg-1 i.p. produced slight inhibition of basal ACh release (by 19%) only in the second sample after i.p. injection. In addition, we also examined the pharmacological mechanisms mediating the interaction between propofol and a gamma-aminobutyric acid A (GABAA) receptor complex. In the rat hippocampus, local application of bicuculline 1 mumol litre-1, a GABAA receptor antagonist, significantly antagonized the inhibitory effects of propofol 50 mg kg-1 i.p. on basal ACh release. In the rat frontal cortex, local application of bicuculline 1 mumol litre-1 did not antagonize the inhibitory effects of propofol 50 mg kg-1 i.p. on basal ACh release, while systemic application of bicuculline 1 mg kg-1 i.p. significantly antagonized the inhibitory effects of propofol 50 mg kg-1 i.p. These results suggest that propofol has powerful depressant effects on ACh release from the rat frontal cortex and hippocampus but not from the striatum, indicating that propofol has a "region-selective" anaesthetic action. Further, these results suggest that the inhibitory effects of propofol in the rat hippocampus may involve "intra" hippocampal GABAA receptors while the inhibitory effects in the rat frontal cortex may be mediated by GABAA receptors other than "intra" frontal cortex GABAA receptors.
我们采用体内微透析技术，研究了丙泊酚对大鼠脑不同区域乙酰胆碱（ACh）释放的影响。腹腔注射25 mg/kg和50 mg/kg的丙泊酚分别使额叶皮质的基础ACh释放量降低了70%和85%。腹腔注射25 mg/kg和50 mg/kg的丙泊酚分别使海马体的基础ACh释放量降低了47%和72%。然而，在大鼠纹状体中，腹腔注射25 mg/kg的丙泊酚对基础ACh释放没有影响，腹腔注射50 mg/kg的丙泊酚仅在注射后的第二个样本中对基础ACh释放产生了轻微抑制（降低了19%）。此外，我们还研究了介导丙泊酚与γ-氨基丁酸A（GABAA）受体复合物相互作用的药理机制。在大鼠海马体中，局部应用1 μmol/L荷包牡丹碱（一种GABAA受体拮抗剂）可显著拮抗腹腔注射50 mg/kg丙泊酚对基础ACh释放的抑制作用。在大鼠额叶皮质中，局部应用1 μmol/L荷包牡丹碱不能拮抗腹腔注射50 mg/kg丙泊酚对基础ACh释放的抑制作用，而腹腔注射1 mg/kg荷包牡丹碱可显著拮抗腹腔注射50 mg/kg丙泊酚的抑制作用。这些结果表明，丙泊酚对大鼠额叶皮质和海马体的ACh释放具有强大的抑制作用，但对纹状体没有影响，这表明丙泊酚具有“区域选择性”麻醉作用。此外，这些结果表明，丙泊酚在大鼠海马体中的抑制作用可能涉及海马体内的GABAA受体，而在大鼠额叶皮质中的抑制作用可能由额叶皮质内GABAA受体以外的GABAA受体介导。
