The role of the agonist binding site in Ca(2+) inhibition of the recombinant 5-HT(3A) receptor.
Eur J Pharmacol
; 428(2): 153-61, 2001 Oct 05.
Article
em En
| MEDLINE
| ID: mdl-11675031
ABSTRACT
The mechanism and site of action of Ca(2+) at the recombinant murine 5-hydroxytryptamine (5-HT)(3A) receptor were investigated using whole-cell voltage clamp, radioligand binding and single-cell Ca(2+) imaging. Inhibition of the 5-HT (3 microM)-induced response by 10 mM Ca(2+) reached a plateau at 68.5% inhibition, with half-maximal effect at 2.6 mM. This was due to an increase in EC(50) from 2.35 to 3.87 microM and a 30% reduction in I(max). Ca(2+) also resulted in the inhibition of binding of both 5-HT(3) receptor agonist [3H]m-chlorophenylbiguanide and antagonist [3H]granisetron due to an increase in K(d), with no change in B(max). An increase in EC(50) from 2.6 (1 mM Ca(2+)) to 4.7 microM (10 mM Ca(2+)), with no change in maximal [Ca(2+)](i), was observed from Ca(2+) imaging studies. Largely similar effects were observed with Mg(2+). The combined data suggest that Ca(2+) acting at a site that directly or indirectly influences the agonist binding site plays a significant role in its inhibitory effect at the 5-HT(3) receptor.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cálcio
/
Receptores de Serotonina
/
Agonistas do Receptor de Serotonina
Limite:
Humans
Idioma:
En
Revista:
Eur J Pharmacol
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Chile