Mutant human α1β1(T262Q) GABAA receptors are directly activated but not modulated by pentobarbital

被引：24

作者：

Dalziel, JE ^{[1
]}

Cox, GB ^{[1
]}

Gage, PW ^{[1
]}

Birnir, B ^{[1
]}

机构：

[1] Australian Natl Univ, John Curtin Sch Med Res, Marine Biol Program, Canberra, ACT 2601, Australia

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 1999年 / 385卷 / 2-3期

关键词：

pentobarbital; ligand-gated; anaesthetic; mutation; GABA(A); receptor; human; (Sf 9) cell;

D O I：

10.1016/S0014-2999(99)00710-4

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Pentobarbital activates GABA(A) receptors and enhances GABA-activated currents. A threonine residue (262) in the second membrane spanning region at the 12' position in the beta(1) subunit, alpha(1)beta(1)(T12'Q), is necessary for the potentiating action of pentobarbital. We examined whether T12'Q-mutated receptors expressed in Spodoptera frugipedra (Sf 9) cells responded to direct activation by pentobarbital. In both mutant and wild type receptors, pentobarbital (100 mu M to 1 mM) evoked a current response. The pentobarbital EC50 values were similar; 119 and 158 mu M for alpha(1)beta(1) and alpha(1)beta(1)(T12'Q) receptors, respectively. The results show it is possible to discriminate between agonistic and potentiating effects of pentobarbital suggesting these actions involve separate mechanisms. (C) 1999 Elsevier Science B.V. All rights reserved.

引用

页码：283 / 286

页数：4

共 19 条

[1] KINETIC-PROPERTIES OF THE PENTOBARBITAL-GATED CHLORIDE CURRENT IN FROG SENSORY NEURONS [J].

AKAIKE, N ;

MARUYAMA, T ;

TOKUTOMI, N .

JOURNAL OF PHYSIOLOGY-LONDON, 1987, 394 :85-98

[2]

Amin J, 1999, MOL PHARMACOL, V55, P411

[3] GABA(A) RECEPTOR NEEDS 2 HOMOLOGOUS DOMAINS OF THE BETA-SUBUNIT FOR ACTIVATION BY GABA BUT NOT BY PENTOBARBITAL [J].

AMIN, J ;

WEISS, DS .

NATURE, 1993, 366 (6455) :565-569

[4] The interaction of the general anesthetic etomidate with the gamma-aminobutyric acid type A receptor is influenced by a single amino acid [J].

Belelli, D ;

Lambert, JJ ;

Peters, JA ;

Wafford, K ;

Whiting, PJ .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (20) :11031-11036

[5] TUBULOINTERSTITIAL NEPHRITIS AND UVEITIS - AN IMMUNOLOGICAL DISORDER [J].

BIRNBACHER, R ;

BALZAR, E ;

AUFRICHT, C ;

SCHMALDIENST, S ;

WOLOSZCZUK, W ;

FORSTER, E .

PEDIATRIC NEPHROLOGY, 1995, 9 (02) :193-195

[6] A structural determinant of desensitization and allosteric regulation by pentobarbitone of the GABA(A) receptor [J].

Birnir, B ;

Tierney, ML ;

Dalziel, JE ;

Cox, GB ;

Gage, PW .

JOURNAL OF MEMBRANE BIOLOGY, 1997, 155 (02) :157-166

[7] The agonistic action of pentobarbital on GABA(A) beta-subunit homomeric receptors [J].

Cestari, IN ;

Uchida, I ;

Li, L ;

Burt, D ;

Yang, J .

NEUROREPORT, 1996, 7 (04) :943-947

[8] Insensitivity to anaesthetic agents conferred by a class of GABA(A) receptor subunit [J].

Davies, PA ;

Hanna, MC ;

Hales, TG ;

Kirkness, EF .

NATURE, 1997, 385 (6619) :820-823

[9]

FORMAN SA, 1995, MOL PHARMACOL, V48, P574

[10]

HORNE AL, 1992, BRIT J PHARMACOL, V107, P732

← 1 2 →