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Propofol acts at the sigma‐1 receptor and inhibits pentazocine‐induced c‐Fos expression in the mouse posterior cingulate and retrosplenial cortices
Author(s) -
Yamada M.,
Nakao S.,
Sakamoto S.,
Takamori Y.,
Tamura Y.,
MochizukiOda N.,
Kataoka Y.,
Yamada H.,
Shingu K.
Publication year - 2006
Publication title -
acta anaesthesiologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.738
H-Index - 107
eISSN - 1399-6576
pISSN - 0001-5172
DOI - 10.1111/j.1399-6576.2006.01033.x
Subject(s) - pentazocine , propofol , agonist , medicine , endocrinology , pharmacology , receptor , c fos , dexmedetomidine , anesthesia , chemistry , analgesic , gene expression , sedation , biochemistry , gene
Background: The sigma‐1 receptor is functionally linked with psychotomimetic effects of various drugs. A sigma‐1 receptor agonist enhances bradykinin‐induced intracellular Ca 2+ concentration ([Ca 2+ ]i) increase and induces c‐Fos expression in a part of the brain. The aim of this study was to investigate the effects of several intravenous anaesthetics on the sigma‐1 receptor. Methods: First, using Wistar rat brains, (+)[ 3 H]SKF‐10,047, a selective sigma‐1 receptor agonist was displaced by propofol, dexmedetomidine, droperidol, and thiopental. Second, Fura‐2 loaded NG‐108 cells were incubated with (+)pentazocine, a selective sigma‐1 receptor agonist, and propofol and then its fluorescence was observed after stimulation with bradykinin. Third, male ICR mice received Intrafat® or propofol intraperitoneally (i.p.), followed by pentazocine i.p. Brain slices were prepared and Fos‐like immunoreactivity was detected using an immunohistochemical method. Results: Propofol, droperidol, and dexmedetomidine displaced (+)[ 3 H]SKF‐10,047 binding in a concentration‐dependent manner with Ki50s of 10.2 ± 0.6, 0.17 ± 0.03, 5.73 ± 1.2 μM, respectively. Thiopental sodium was practically ineffective. Propofol produced a statistically significant reduction in the maximal binding capacity (Bmax) but did not affect the dissociation constant ( K d ). (+)Pentazocine significantly enhanced bradykinin‐induced [Ca 2+ ]i increases, but propofol did not affect it. Pentazocine induced marked Fos‐LI positive cells in the posterior cingulate and retrosplenial cortices (PC/RS), which was significantly reduced by propofol. Conclusions: These results suggest that propofol may be a sigma‐1 receptor antagonist, and that various effects of propofol on the brain may be mediated, at least partly, by the sigma‐1 receptor.