[Effects of general anesthetics on neuronal nicotinic acetylcholine receptors and their roles in the mechanism of anesthesia].
Neuronal nicotinic acetylcholine receptors (nAchRs) are widely expressed in the central and autonomic nervous systems and have subunit compositions with biophysical and pharmacological properties distinct from those of the receptors at the neuromuscular junction. They are thought to modulate synaptic transmission in the central nervous system (CNS) mainly by regulating the release of neurotransmitters. Although roles of neuronal nAchRs in the CNS are poorly understood, these receptors are involved in cognitive performance, nociception and psychoneurological disorders such as Alzheimer's and Parkinson disease. It is known that both central and peripheral neuronal nAchRs are sensitive to various types of anesthetics. Among those, barbiturates, ketamine, volatile and gaseous anesthetics depress neuronal nAchRs at or below clinical concentrations. Inhibition of neuronal nAchRs by barbiturates is unlikely to contribute to the anesthetic action of barbiturates, since this effect does not correlate with the anesthetic potencies of barbiturate stereoisomers. Relevance of inhibition of these receptors is controversial for anesthetic effects of other anesthetics, because conflicting results have been obtained from comparison of this effect with anesthetic actions of stereoisomers or structurally related compounds. However, it is possible that inhibition of central nAchRs contributes to secondary effects attributed to anesthesia such as impairment in memory and cognitive performance.
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Department of Anesthesiology, Yokohama City University School of Medicine, Yokohama 236-0004.
D000758:Anesthesia; D018681:Anesthetics, General / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D003072:Cognition Disorders / Q000139:chemically induced; D006801:Humans; D008569:Memory Disorders / Q000139:chemically induced; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission
D018681:Anesthetics, General; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic