[Orexinergic neurons and noradrenergic awakening system in general anesthesia].
The sleep-wake cycle is regulated by interaction between monoaminergic, cholinergic and GABAergic neuronal activities. Monoaminergic neurons including noradrenergic (locus coeruleus: LC), histaminergic (tuberomammillary nucleus) and serotonergic (raphe nuclei) neurons projected diffusely to the cerebrocortex, thalamus and brainstem are known as the center of sleep regulation. Interestingly, although the cell bodies displaying prepro-orexin (prepro-OX) immunoreactivity are limited to the hypothalamus, OXergic neurons densely project to LC, tuberomammillary nucleus and raphe nuclei. These evidences suggest a link between monoaminergic and OXergic neurons. We found that OXA and B evoke norepinephrine release from rat cerebrocortical slices but histamine and serotonin releases are not evoked. All noradrenergic projections to cerebrocortex originate from the LC. Thus, the main link between OXergic and monoaminergic neurons may be noradrenergic in the cerebral cortex. Therefore, we have studied OXergic-noradrenergic neurons and anesthesia. We found that OXs reduced anesthesia time, which was reversed by SB334867 (OX1-receptor antagonist). However, as alpha2-receptor ligands did not affect OXs-norepinephrine release from cerebrocortical slices, alpha2-receptors may not be involved in OXergic-noradrenergic neurons in the cerebral cortex. Bicuculline (GABAA-receptor antagonist) could not reverse inhibitory effects of barbiturates on OXs-norepinephrine release but significantly reversed these effects on K+-evoked release. Moreover, muscimol (GABAA-receptor agonist) did not inhibit the OX-norepinephrine release but inhibited the K+-evoked release. Therefore, GABAA-receptor may also not be involved.
Hirota
Kazuyoshi
K
Department of Anesthesiology, University of Hirosaki School of Medicine, Hirosaki 036-8562.
D000762:Anesthesia Recovery Period; D000768:Anesthesia, General; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D009479:Neuropeptides / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism / Q000502:physiology*; D000068797:Orexins; D051381:Rats; D013997:Time Factors; D014851:Wakefulness / Q000502:physiology*
D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D009638:Norepinephrine