Seeman Philip, Kapur Shitij
Department of Pharmacology, University of Toronto, Toronto, Ontario M5S JA8, Canada.
Synapse. 2003 Oct;50(1):35-40. doi: 10.1002/syn.10221.
The high-affinity states of dopamine D2 and D3 receptors, serotonin 5HT-2A receptors, beta-2-adrenoceptors, alpha-1 and alpha-2 adrenoceptors, opiate receptors, and muscarinic receptors were inhibited by clinical concentrations of anesthetics, including isoflurane, halothane, chloral hydrate, ketamine, and ethanol. The inhibition occurred not only in vitro, but also in vivo in rats anesthetized with isoflurane, with the high-affinity states recovering at different rates. Because the high-affinity states of G-protein-linked receptors are physiologically functional, their general inhibition by clinical concentrations of anesthetics may underlie general anesthesia and may explain some of the side effects of anesthetics. Subanesthetic concentrations of the anesthetics, including ketamine, stimulated the incorporation of GTP into the cloned dopamine D2 receptors. It is possible that the classical stage 2 excitement phase which occurs with subanesthetic concentrations of general anesthetics and ketamine may be associated with this general stimulation of a variety of G-protein-linked receptors, as found in the present study, while the stage 3 level of surgical anesthesia may be associated with the inhibition of the high-affinity states of several receptors.
包括异氟烷、氟烷、水合氯醛、氯胺酮和乙醇在内的临床麻醉药浓度可抑制多巴胺D2和D3受体、5-羟色胺5HT-2A受体、β-2肾上腺素能受体、α-1和α-2肾上腺素能受体、阿片受体以及毒蕈碱受体的高亲和力状态。这种抑制不仅在体外发生，在用异氟烷麻醉的大鼠体内也会出现，且高亲和力状态以不同速率恢复。由于G蛋白偶联受体的高亲和力状态具有生理功能，临床麻醉药浓度对其产生的普遍抑制可能是全身麻醉的基础，并且可以解释麻醉药的一些副作用。包括氯胺酮在内的亚麻醉药浓度可刺激GTP掺入克隆的多巴胺D2受体。正如本研究中所发现的那样，全身麻醉药和氯胺酮的亚麻醉药浓度所引发的经典兴奋期2阶段可能与多种G蛋白偶联受体的这种普遍刺激有关，而外科麻醉的3阶段水平可能与几种受体高亲和力状态的抑制有关。
