RRC ID |
39437
|
著者 |
Yamashita M, Ikemoto Y, Nielsen M, Yano T.
|
タイトル |
Effects of isoflurane and hexafluorodiethyl ether on human recombinant GABA(A) receptors expressed in Sf9 cells.
|
ジャーナル |
Eur J Pharmacol
|
Abstract |
Effects of volatile anesthetics and a volatile convulsant on human recombinant gamma-aminobutyric acid (GABA) type A receptor responses were studied using the whole cell configuration of the patch clamp technique. Sf9 cells were transfected with bacuroviruses carrying cDNAs of alpha1beta2, alpha1beta2gamma2s, alpha3beta2 and alpha3beta2gamma2s subunit combinations of the human GABA(A) receptor. Clinical concentrations of isoflurane (a volatile anesthetic) enhanced the GABA-induced current of the alpha1beta2gamma2s and alpha3beta2gamma2s GABA(A) subunit combinations. On the other hand, isoflurane suppressed the current of the alpha1beta2 and alpha3beta2 subunit combinations, indicating that the anesthetic effects depended upon the presence of gamma2s subunit. A high concentration (2 mM) of isoflurane generated a surge current following the washout of GABA and the anesthetic. Hexafluorodiethyl ether (a volatile convulsant) decreased the GABA-response of the both alpha3beta2gamma2s and alpha3beta2 constructs without generating a surge current. The results suggest that volatile agents affect the receptor-ionophore complex via direct interaction with proteins but not through a perturbation of the membrane lipid environment. A hypothetical sequential model for the anesthetic action is presented.
|
巻・号 |
378(2)
|
ページ |
223-31
|
公開日 |
1999-8-6
|
DOI |
10.1016/s0014-2999(99)00468-9
|
PII |
S0014-2999(99)00468-9
|
PMID |
10478635
|
MeSH |
Anesthetics, Inhalation / pharmacology*
Cells, Cultured
Convulsants / pharmacology*
DNA, Complementary / genetics*
Dose-Response Relationship, Drug
Drug Interactions
Flurothyl / pharmacology*
Humans
Isoflurane / pharmacology*
Patch-Clamp Techniques
Receptors, GABA-A / drug effects*
Recombinant Proteins
gamma-Aminobutyric Acid / chemistry
gamma-Aminobutyric Acid / pharmacology*
|
IF |
3.263
|
引用数 |
8
|
WOS 分野
|
PHARMACOLOGY & PHARMACY
|
リソース情報 |
ヒト・動物細胞 |
|