CHIMERIC NICOTINIC SEROTONERGIC RECEPTOR COMBINES DISTINCT LIGAND-BINDING AND CHANNEL SPECIFICITIES

被引：345

作者：

EISELE, JL ^{[1
]}

BERTRAND, S ^{[1
]}

GALZI, JL ^{[1
]}

DEVILLERSTHIERY, A ^{[1
]}

CHANGEUX, JP ^{[1
]}

BERTRAND, D ^{[1
]}

机构：

[1] UNIV GENEVA, MED CTR, FAC MED, DEPT PHYSIOL, CH-1211 GENEVA 4, SWITZERLAND

来源：

NATURE | 1993年 / 366卷 / 6454期

关键词：

D O I：

10.1038/366479a0

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

THE neuronal nicotinic alpha7 (nAChR) and 5-hydroxytryptamine (5HT3) receptors1-3 are ligand-gated ion channels with a homologous topological organization and have activation and desensitization reactions in common. Yet these homo-oligomeric receptors differ in the pharmacology of their binding sites for agonists and competitive antagonists3,4, and in their sensitivity to Ca2+ ions. The alpha7 channel is highly permeable to Ca2+ ions5,6 and external Ca2+ ions potentiate, in an allosteric manner, the permeability response to acetylcholine, as shown for other neuronal nAChRs7,8. The 5HT3 channel, in contrast, is not permeable to Ca2+ ions, but blocked by them3,9. To assign these properties to delimited domains of the primary structure, we constructed several recombinant chimaeric alpha7-5HT3 receptors. We report here that one of the constructs expresses a functional receptor that contains the serotonergic channel still blocked by Ca2+ ions, but is activated by nicotinic ligands and potentiated by external Ca2+ ions.

引用

页码：479 / 483

页数：5

共 35 条

[1] PHARMACOLOGICAL PROPERTIES OF THE HOMOMERIC ALPHA-7 RECEPTOR [J].

BERTRAND, D ;

BERTRAND, S ;

BALLIVET, M .

NEUROSCIENCE LETTERS, 1992, 146 (01) :87-90

[2] MUTATIONS AT 2 DISTINCT SITES WITHIN THE CHANNEL DOMAIN M2 ALTER CALCIUM PERMEABILITY OF NEURONAL ALPHA-7 NICOTINIC RECEPTOR [J].

BERTRAND, D ;

GALZI, JL ;

DEVILLERSTHIERY, A ;

BERTRAND, S ;

CHANGEUX, JP .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (15) :6971-6975

[3]

BERTRAND D, 1991, ELECTROPHYSIOLOGY NE

[4] PROPOSALS FOR THE CLASSIFICATION AND NOMENCLATURE OF FUNCTIONAL RECEPTORS FOR 5-HYDROXYTRYPTAMINE [J].

BRADLEY, PB ;

ENGEL, G ;

FENIUK, W ;

FOZARD, JR ;

HUMPHREY, PPA ;

MIDDLEMISS, DN ;

MYLECHARANE, EJ ;

RICHARDSON, BP ;

SAXENA, PR .

NEUROPHARMACOLOGY, 1986, 25 (06) :563-576

[5] NUCLEOTIDE AND DEDUCED AMINO-ACID-SEQUENCES OF TORPEDO-CALIFORNICA ACETYLCHOLINE-RECEPTOR GAMMA-SUBUNIT [J].

CLAUDIO, T ;

BALLIVET, M ;

PATRICK, J ;

HEINEMANN, S .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1983, 80 (04) :1111-1115

[6] A NEURONAL NICOTINIC ACETYLCHOLINE-RECEPTOR SUBUNIT (ALPHA-7) IS DEVELOPMENTALLY REGULATED AND FORMS A HOMOOLIGOMERIC CHANNEL BLOCKED BY ALPHA-BTX [J].

COUTURIER, S ;

BERTRAND, D ;

MATTER, JM ;

HERNANDEZ, MC ;

BERTRAND, S ;

MILLAR, N ;

VALERA, S ;

BARKAS, T ;

BALLIVET, M .

NEURON, 1990, 5 (06) :847-856

[7] AMINO-ACIDS OF THE TORPEDO-MARMORATA ACETYLCHOLINE-RECEPTOR ALPHA-SUBUNIT LABELED BY A PHOTOAFFINITY LIGAND FOR THE ACETYLCHOLINE BINDING-SITE [J].

DENNIS, M ;

GIRAUDAT, J ;

KOTZYBAHIBERT, F ;

GOELDNER, M ;

HIRTH, C ;

CHANG, JY ;

LAZURE, C ;

CHRETIEN, M ;

CHANGEUX, JP .

BIOCHEMISTRY, 1988, 27 (07) :2346-2357

[8] COMPLETE MESSENGER-RNA CODING SEQUENCE OF THE ACETYLCHOLINE BINDING ALPHA-SUBUNIT OF TORPEDO-MARMORATA ACETYLCHOLINE-RECEPTOR - A MODEL FOR THE TRANSMEMBRANE ORGANIZATION OF THE POLYPEPTIDE-CHAIN [J].

DEVILLERSTHIERY, A ;

GIRAUDAT, J ;

BENTABOULET, M ;

CHANGEUX, JP .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1983, 80 (07) :2067-2071

[9]

GALZI JL, 1990, J BIOL CHEM, V265, P10430

[10] MUTATIONS IN THE CHANNEL DOMAIN OF A NEURONAL NICOTINIC RECEPTOR CONVERT ION SELECTIVITY FROM CATIONIC TO ANIONIC [J].

GALZI, JL ;

DEVILLERSTHIERY, A ;

HUSSY, N ;

BERTRAND, S ;

CHANGEUX, JP ;

BERTRAND, D .

NATURE, 1992, 359 (6395) :500-505

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