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Titolo:
DETERMINANTS OF COMPETITIVE ANTAGONIST SENSITIVITY ON NEURONAL NICOTINIC RECEPTOR-BETA SUBUNITS
Autore:
HARVEY SC; LUETJE CW;
Indirizzi:
UNIV MIAMI,SCH MED,DEPT MOLEC & CELLULAR PHARMACOL,POB 016189 MIAMI FL 33101 UNIV MIAMI,SCH MED,DEPT MOLEC & CELLULAR PHARMACOL MIAMI FL 33101
Titolo Testata:
The Journal of neuroscience
fascicolo: 12, volume: 16, anno: 1996,
pagine: 3798 - 3806
SICI:
0270-6474(1996)16:12<3798:DOCASO>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACETYLCHOLINE BINDING-SITE; ALPHA-SUBUNIT; DELTA-SUBUNIT; AGONIST SELECTIVITY; IDENTIFICATION; CONTRIBUTE; RESIDUES; LIGAND; INTERFACES; DIVERSITY;
Keywords:
NICOTINIC RECEPTOR; NEURONAL; ANTAGONISTS; MUTANT; CHIMERA; NEURONAL BUNGAROTOXIN; DIHYDRO-BETA-ERYTHROIDINE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Physical, Chemical & Earth Sciences
Science Citation Index Expanded
Citazioni:
38
Recensione:
Indirizzi per estratti:
Citazione:
S.C. Harvey e C.W. Luetje, "DETERMINANTS OF COMPETITIVE ANTAGONIST SENSITIVITY ON NEURONAL NICOTINIC RECEPTOR-BETA SUBUNITS", The Journal of neuroscience, 16(12), 1996, pp. 3798-3806

Abstract

We constructed a series of chimeric and mutant neuronal nicotinic acetylcholine receptor beta subunits to map amino acid residues that determine sensitivity to competitive antagonists. The beta 2 and beta 4 subunits form pharmacologically distinct receptors when expressed in combination with the alpha 3 subunit in Xenopus oocytes. At equipotent acetylcholine concentrations, alpha 3 beta 2 is 56-fold more sensitive to blockade by dihydro-beta-erythroidine than is alpha 3 beta 4. The alpha 3 beta 2 combination is also sensitive to long-term blockade by neuronal bungarotoxin, whereas alpha 3 beta 4 is not. Pharmacological analysis of receptors formed by chimeric beta subunits reveals that amino acid residues that determine both dihydro-beta-erythroidine and neuronal bungarotoxin sensitivity are located within several sequence segments. The major determinant of sensitivity to both competitive antagonists is located between residues 54 and 63. A minor determinant of sensitivity to both antagonists lies between residues 1 and 54, whereas aminor determinant of NET sensitivity lies between residues 74 and 80. Within region 54-63 of beta 2, mutant beta 2 subunits were used to identify threonine 59 as a residue critical in determining competitive antagonist sensitivity, Changing threonine 59 to lysine, as occurs in beta 4, causes a 9-fold decrease in dihydro-beta-erythroidine sensitivity and a 71-fold decrease in neuronal bungarotoxin sensitivity. Changing polar threonine 59 to negatively charged aspartate causes a 2.5-foId increase in neuronal bungarotoxin sensitivity and has no effect on dihydro-beta-erythroidine sensitivity.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/07/20 alle ore 23:08:11