Alpha-bungarotoxin binding and central nervous system nicotinic acetylcholine receptors

Neuroscience ◽  
1981 ◽  
Vol 6 (1) ◽  
pp. 1-14 ◽  
Author(s):  
R.E. Oswald ◽  
J.A. Freeman
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Nicotinic Acetylcholine ◽  
Alpha Bungarotoxin

Alpha4beta2 Neuronal Nicotinic Acetylcholine Receptors in the Central Nervous System Are Inhibited by Isoflurane and Propofol, but alpha7-type Nicotinic Acetylcholine Receptors Are Unaffected 

1997 ◽  
Vol 86 (4) ◽  
pp. 859-865 ◽  
Author(s):  
Pamela Flood ◽  
Jose Ramirez-Latorre ◽  
Lorna Role
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
General Anesthetics ◽  
Nicotinic Acetylcholine ◽  
The Central Nervous System ◽  
Beta 2 ◽  
Alpha 7

Background The mechanisms of action of general anesthetics are not completely understood. Many general anesthetics are reported to potentiate gamma-aminobutyric acid (GABAA) and glycine receptors in the central nervous system (CNS) and to inhibit the muscle-type nicotinic acetylcholine receptor (nAChR). The effects of general anesthetics on another family of ligand-gated ion channel in the CNS, the nAChRs, have not been defined. Methods Two types of CNS acetylcholine receptor, the alpha 4 beta 2 receptor or the alpha 7 homomeric receptor, were expressed heterologously in Xenopus laevis oocytes. Using the standard two-microelectrode voltage-clamp technique, peak acetylcholinegated current was measured before and after coapplication of isoflurane or propofol. Results Coapplication of either isoflurane or propofol with acetylcholine resulted in potent, dose-dependent inhibition of the alpha 4 beta 2 receptor current with median inhibitory concentrations of 85 and 19 microM, respectively. The inhibition of the alpha 4 beta 2 receptor by both isoflurane and propofol appears to be competitive with respect to acetylcholine. The alpha 7 receptor current was not effected by either anesthetic. Conclusions The CNS-type nAChRs are differentially affected by isoflurane and propofol. The alpha 4 beta 2 receptor is affected by isoflurane more potently than the most sensitive GABAA or glycine receptor that has been reported, whereas the alpha 7 homomeric receptor is not affected by either anesthetic. Inhibition of specific subtypes of nAChRs in the CNS, along with potentiation of GABAA and glycine receptors, may contribute to the effects and side effects of general anesthetics.

Inhibitory Effects of Barbiturates on Nicotinic Acetylcholine Receptors in Rat Central Nervous System Neurons

2001 ◽  
Vol 94 (4) ◽  
pp. 694-704 ◽  
Author(s):  
Yoshinori Kamiya ◽  
Tomio Andoh ◽  
Itaru Watanabe ◽  
Tomoko Higashi ◽  
Hideki Itoh
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Pc12 Cells ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Induced Current ◽  
Nicotinic Acetylcholine ◽  
Current Decay ◽  
Medial Habenula ◽  
Significant Difference

Background Neuronal nicotinic acetylcholine receptors (nAChRs) are widely expressed in the central and autonomic nervous systems. The authors have previously shown that depressant and convulsant barbiturates both inhibit the ganglion-type nAchRs in PC12 cells. However, the central and gangliontype receptors have different subunit composition and pharmacologic properties. In this study, the authors investigated the effects of thiopental, depressant [R(-)] and convulsant [S(+)] stereoisomers of 1-methyl-5 phenyl-5-propyl barbituric acid (MPPB) on neuronal nAChRs in the rat central nervous system to explore significance of these effects in barbiturate anesthesia. Methods Whole-cell currents were measured in acutely dissociated rat medial habenula (MHb) neurons by applying 10 or 100 microM nicotine in the absence or presence of thiopental 3-100 microM. Effects of R(-)- and S(+)-MPPB on the nicotine-induced current were also studied. Results Thiopental suppressed the nicotine-elicited inward current and accelerated the current decay dose-dependently at the clinical relevant concentrations. R(-)- and S(+)-MPPB both inhibited the nicotine-induced current dose-dependently without augmenting the current decay. There was no significant difference in the magnitudes of inhibition by R(-)- and S(+)-MPPB. Conclusions Although thiopental suppressed the current mediated through native nAchRs in rat MHb neurons at the clinically relevant concentrations, the depressant and convulsant stereoisomers of MPPB both inhibited the current in the same extent. These findings are consistent with the results previously obtained in the ganglion-type receptors of PC12 cells and suggest that inhibition of nAChRs in MHb neurons is not directly relevant to the hypnotic or anticonvulsive actions of barbiturates.

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