Interactions of agonists with an allosteric antagonist at muscarinic acetylcholine M2 receptors.
Eur J Pharmacol
; 316(1): 27-32, 1996 Nov 28.
Article
em En
| MEDLINE
| ID: mdl-8982646
ABSTRACT
The interaction of heptane-1,7-bis(dimethyl-3'-phthalimidopropylammonium bromide) (C7/3'-phth), with several agonists, was investigated at the muscarinic M2 receptor in guinea-pig left atria. C7/3'-phth shifted concentration-response curves for the agonists, carbachol, oxotremorine-M and (+)-cis-dioxolane, to the right in a parallel fashion. Arunlakshana-Schild regressions of the data yielded slopes significantly different to unity, suggesting non-competitive antagonism. Non-linear regression analysis, using an equation based on allosteric modulation, gave quantitative estimates of co-operativity (alpha values) and the dissociation constant of C7/3'-phth (KB). In all cases, the KB estimates for C7/3'-phth were not significantly different. Increasing the carbachol contact time 10-fold did not significantly influence the KB or the alpha value obtained with C7/3'-phth. Changing from Krebs to Tyrode solution did not significantly alter the KB for C7/3'-phth, although alpha values obtained were consistently lower in Tyrode solution, suggesting that the allosteric action may be sensitive to buffer composition. A 4-fold higher degree of negative, heterotropic co-operativity between C7/3'-phth and agonists than between C7/3'-phth and competitive antagonists was also found.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores Muscarínicos
/
Antagonistas Muscarínicos
/
Agonistas Muscarínicos
/
Compostos de Bis-Trimetilamônio
Limite:
Animals
Idioma:
En
Revista:
Eur J Pharmacol
Ano de publicação:
1996
Tipo de documento:
Article