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Anesthetics inhibit high‐affinity states of dopamine D2 and other G‐linked receptors
Author(s) -
Seeman Philip,
Kapur Shitij
Publication year - 2003
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.10221
Subject(s) - chemistry , receptor , halothane , pharmacology , isoflurane , dopamine , stimulation , dopamine receptor d2 , dopamine receptor , 5 ht receptor , d2 like receptor , serotonin , medicine , biochemistry , biology , dopamine receptor d1 , organic chemistry
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. Synapse 50:35–40, 2003. © 2003 Wiley‐Liss, Inc.