TY - JOUR
T1 - Modulation of the Benzodiazepine/γ‐Aminobutyric Acid Receptor Chloride Channel Complex by Inhalation Anesthetics
AU - Moody, Eric J.
AU - Suzdak, P. D.
AU - Paul, S. M.
AU - Skolnick, P.
PY - 1988/11
Y1 - 1988/11
N2 - Abstract: Inhalation anesthetics, such as diethyl ether, halo‐thane, and enflurane, increase 36C1− uptake into rat cerebral cortical synaptoneurosomes in a concentration‐dependent, picrotoxin‐sensitive fashion. At concentrations consistent with those that stimulate 36C1− uptake, inhalation anesthetics also inhibit the binding of t‐[35S]butylbicyclophosphoro‐thionate ([35S]TBPS) to well‐washed cortical membranes. Scatchard analysis of [35S]TBPS binding indicates that these agents reduce the apparent affinity of this radioligand and have little effect on the Bmax. The ability of inhalation anesthetics to directly stimulate 36C1− uptake and inhibit [35S]TBPS binding is a property shared by nonvolatile anesthetics. Nonetheless, there are differences between nonvolatile agents (such as barbiturates and alcohols) and in halation anesthetics, because the former compounds augment muscimol (a GABAmimetic) stimulated 36C1− uptake, whereas the latter group (such as ether and enflurane) inhibit this effect. These findings demonstrate that therapeutically relevant concentrations of inhalation anesthetics perturb the benzodiazepine/γ‐aminobutyric acid receptor chloride channel complex, and suggest this oligomeric protein may be a common mediator of some aspects of anesthetic action.
AB - Abstract: Inhalation anesthetics, such as diethyl ether, halo‐thane, and enflurane, increase 36C1− uptake into rat cerebral cortical synaptoneurosomes in a concentration‐dependent, picrotoxin‐sensitive fashion. At concentrations consistent with those that stimulate 36C1− uptake, inhalation anesthetics also inhibit the binding of t‐[35S]butylbicyclophosphoro‐thionate ([35S]TBPS) to well‐washed cortical membranes. Scatchard analysis of [35S]TBPS binding indicates that these agents reduce the apparent affinity of this radioligand and have little effect on the Bmax. The ability of inhalation anesthetics to directly stimulate 36C1− uptake and inhibit [35S]TBPS binding is a property shared by nonvolatile anesthetics. Nonetheless, there are differences between nonvolatile agents (such as barbiturates and alcohols) and in halation anesthetics, because the former compounds augment muscimol (a GABAmimetic) stimulated 36C1− uptake, whereas the latter group (such as ether and enflurane) inhibit this effect. These findings demonstrate that therapeutically relevant concentrations of inhalation anesthetics perturb the benzodiazepine/γ‐aminobutyric acid receptor chloride channel complex, and suggest this oligomeric protein may be a common mediator of some aspects of anesthetic action.
KW - Anesthetics
KW - Chloride uptake
KW - Enflurane
KW - Ether
KW - t‐Butylbicyclophosphorothionate
KW - γ‐Aminobutyric acid
UR - http://www.scopus.com/inward/record.url?scp=0023781498&partnerID=8YFLogxK
U2 - 10.1111/j.1471-4159.1988.tb01102.x
DO - 10.1111/j.1471-4159.1988.tb01102.x
M3 - Article
C2 - 2459308
AN - SCOPUS:0023781498
SN - 0022-3042
VL - 51
SP - 1386
EP - 1393
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 5
ER -