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Abstract:

In the present study, we provide evidence that the α9 nicotinic acetylcholine receptor (nAChR) shares pharmacological properties with members of the Cys-loop family of receptors. Thus, the type A γ-aminobutyric acid receptor antagonist bicuculline, the glycinergic antagonist strychnine, and the type 3 serotonin receptor antagonist ICS-205,930 block ACh-evoked currents in α9-injected Xenopus laevis oocytes with the following rank order of potency: strychnine > ICS-205,930 > bicuculline. Block by antagonists was reflected in an increase in the acetylcholine (ACh) EC50 value, with no changes in agonist maximal response or Hill coefficient, which suggests a competitive type of block. Moreover, whereas neither γ-aminobutyric acid nor glycine modified ACh-evoked currents, serotonin blocked responses to ACh in a concentration-dependent manner. The present results suggest that the α9 nAChR must conserve in its primary structure some residues responsible for ligand binding common to other Cys-loop receptors. In addition, it adds further evidence that the α9 nAChR and the cholinergic receptor present at the base of cochlear outer hair cells have similar pharmacological properties.

Registro:

Documento: Artículo
Título:The α9 nicotinic acetylcholine receptor shares pharmacological properties with type A γ-aminobutyric acid, glycine, and type 3 serotonin receptors
Autor:Rothlin, C.V.; Katz, E.; Verbitsky, M.; Belén Elgoyhen, A.
Filiación:Inst. Invest. Ing. Genet. Biol. M., Consejo Natl. de Invest. Cie., Tec.-Fac. de Cie. Exactes Nat., Buenos Aires, Argentina
Departamento de Biología, Fac. de Ciencias Exactes Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Inst. Invest. en Ing. Genet. Biol., Molecular (CONICET-UBA), Obligado 2490, Buenos Aires 1428, Argentina
Palabras clave:4 aminobutyric acid; 4 aminobutyric acid A receptor; 4 aminobutyric acid A receptor blocking agent; acetylcholine; bicuculline; cysteine; ethylene glycol 1,2 bis(2 aminophenyl) ether n,n,n',n' tetraacetic acid; glycine; glycine receptor; glycine receptor antagonist; ligand; nicotinic receptor; receptor blocking agent; serotonin 3 antagonist; serotonin 3 receptor; strychnine; tropisetron; 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; 4 aminobutyric acid A receptor; 4 aminobutyric acid receptor blocking agent; amino acid receptor affecting agent; barium; bicuculline; calcium; chelating agent; complementary DNA; drug derivative; egtazic acid; glycine receptor; hybrid protein; Indo 1 pentaacetoxymethyl ester; Indo-1 pentaacetoxymethyl ester; indole derivative; nicotinic receptor; serotonin; serotonin 3 receptor; serotonin antagonist; serotonin receptor; strychnine; tropisetron; animal cell; article; competitive inhibition; concentration response; controlled study; hair cell; ligand binding; nonhuman; oocyte; priority journal; receptor binding; Xenopus; animal; cell membrane potential; drug effect; female; genetics; metabolism; Xenopus laevis; Acetylcholine; Animals; Barium; Bicuculline; Calcium; Chelating Agents; DNA, Complementary; Egtazic Acid; Female; GABA Antagonists; Glycine; Glycine Agents; Indoles; Membrane Potentials; Oocytes; Receptors, GABA-A; Receptors, Glycine; Receptors, Nicotinic; Receptors, Serotonin; Receptors, Serotonin, 5-HT3; Recombinant Fusion Proteins; Serotonin; Serotonin Antagonists; Strychnine; Xenopus laevis
Año:1999
Volumen:55
Número:2
Página de inicio:248
Página de fin:254
DOI: http://dx.doi.org/10.1124/mol.55.2.248
Título revista:Molecular Pharmacology
Título revista abreviado:Mol. Pharmacol.
ISSN:0026895X
CODEN:MOPMA
CAS:4 aminobutyric acid, 28805-76-7, 56-12-2; acetylcholine, 51-84-3, 60-31-1, 66-23-9; bicuculline, 485-49-4; cysteine, 4371-52-2, 52-89-1, 52-90-4; ethylene glycol 1,2 bis(2 aminophenyl) ether n,n,n',n' tetraacetic acid, 73630-08-7; glycine, 56-40-6, 6000-43-7, 6000-44-8; strychnine, 1421-86-9, 57-24-9; tropisetron, 89565-68-4; 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, 85233-19-8; Acetylcholine, 51-84-3; Barium, 7440-39-3; Bicuculline, 485-49-4; Calcium, 7440-70-2; Chelating Agents; DNA, Complementary; Egtazic Acid, 67-42-5; GABA Antagonists; Glycine Agents; Glycine, 56-40-6; Indo-1 pentaacetoxymethyl ester, 112926-02-0; Indoles; Receptors, GABA-A; Receptors, Glycine; Receptors, Nicotinic; Receptors, Serotonin; Receptors, Serotonin, 5-HT3; Recombinant Fusion Proteins; Serotonin Antagonists; Serotonin, 50-67-9; Strychnine, 57-24-9; tropisetron, 89565-68-4
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0026895X_v55_n2_p248_Rothlin

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Citas:

---------- APA ----------
Rothlin, C.V., Katz, E., Verbitsky, M. & Belén Elgoyhen, A. (1999) . The α9 nicotinic acetylcholine receptor shares pharmacological properties with type A γ-aminobutyric acid, glycine, and type 3 serotonin receptors. Molecular Pharmacology, 55(2), 248-254.
http://dx.doi.org/10.1124/mol.55.2.248
---------- CHICAGO ----------
Rothlin, C.V., Katz, E., Verbitsky, M., Belén Elgoyhen, A. "The α9 nicotinic acetylcholine receptor shares pharmacological properties with type A γ-aminobutyric acid, glycine, and type 3 serotonin receptors" . Molecular Pharmacology 55, no. 2 (1999) : 248-254.
http://dx.doi.org/10.1124/mol.55.2.248
---------- MLA ----------
Rothlin, C.V., Katz, E., Verbitsky, M., Belén Elgoyhen, A. "The α9 nicotinic acetylcholine receptor shares pharmacological properties with type A γ-aminobutyric acid, glycine, and type 3 serotonin receptors" . Molecular Pharmacology, vol. 55, no. 2, 1999, pp. 248-254.
http://dx.doi.org/10.1124/mol.55.2.248
---------- VANCOUVER ----------
Rothlin, C.V., Katz, E., Verbitsky, M., Belén Elgoyhen, A. The α9 nicotinic acetylcholine receptor shares pharmacological properties with type A γ-aminobutyric acid, glycine, and type 3 serotonin receptors. Mol. Pharmacol. 1999;55(2):248-254.
http://dx.doi.org/10.1124/mol.55.2.248