EFFECTS OF ANESTHETICS ON TRANSMISSION IN CNS

众所周知，全身麻醉药增加了中枢神经系统的GABA-A反应，导致抑制传递的增强。人重组GABA-A受体在Sf9细胞中表达，并发现异氟醚的亚基特异性效应，表明挥发性麻醉剂与膜通道蛋白相互作用诱导人类麻醉。在这些神经元的电压钳下，记录微型EPSCs。异氟醚增加了甘氨酸能mIPSC的频率，而不是幅度。外源钙离子的存在和不存在均使细胞外钙离子浓度增加，提示外周和中枢神经系统内钙离子浓度的增加是通过细胞内钙离子的释放而实现的。在大鼠背根神经节神经元中，我们发现了分别由P2X2和P2X3受体亚型激活引起的慢和快衰减的ATP电流。氯胺酮对ATP电流无影响。异丙酚可降低快型电流的峰值，加速慢型电流的衰减。戊巴比妥对快型电流的抑制作用强于慢型电流。在酸性较弱的环境中，还原作用较大，表明药物的电离形式是造成这种效果的原因。帕拉本甲酯作为防腐剂存在于牙科用局部麻醉药筒中。对羟基苯甲酸甲酯增加大鼠腹膜肥大细胞内浓度可能是通过产生IP3实现的。当PKA以某种方式被激活时，该试剂促进肥大细胞释放组胺。这一发现表明，在临床实践中，对羟基苯甲酸甲酯可能会引起类过敏反应。

It is known that general anesthetics increase the GABA-A response in the CNS, resulting in augmentation of inhibitory transmission. Human recombinant GABA-A receptors were expressed in Sf9 cells and subunit specific effects of isoflurane were found, indicating that volatile anesthetics interact with membrane channel proteins to induce anesthesia in humans.We dissociated central neurons of the rat, which had presysaptic terminals (boutons) attached. Under voltage clamp of these neurons, miniature EPSCs were recorded. Isoflurane increased the frequency, not amplitude of the glycinergic mIPSC. The increase was observed in both the presence and absence of external calcium ions, suggesting that the calcium concentration in the bouton was increased via release from the intracellular store sites.ATP acts as an excitatory neurotransmitter via P2X receptors in peripheral and central nervous system. In DRG neurons of the rat, we identified slow and fast decaying ATP currents, which were due to activation of P2X2 and P2X3 receptor subtypes, respectively. Ketamine had no effects on the ATP currents. Propofol reduced the peak amplitude of the fast type current and accelerated the decay of the slow type current in the presence of ATP. Pentobarbital decreased the fast type current more potently than the slow type. The reduction was greater in less acidic environment, suggesting that ionized form of the agent was responsible for the effect.Methyl paraben is contained as preservative in local anesthetic cartridges for dental use. Methyl paraben increased the intracellular concentration of rat peritoneal mast cells, probably via IP3 production. When PKA was activated somehow, the agent enhanced the release of histamine from the mast cells. This finding suggests that methyl paraben may induce anaphylactoid reactions in clinical practice.