Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...
On the interaction of gallamine with muscarinic receptor subtypes
Ist Teil von
European journal of pharmacology, 1990-07, Vol.182 (2), p.335-345
Ort / Verlag
Amsterdam: Elsevier B.V
Erscheinungsjahr
1990
Quelle
Elsevier Journal Backfiles on ScienceDirect (DFG Nationallizenzen)
Beschreibungen/Notizen
The interaction of gallamine with muscarinic receptor subtypes was examined using radioligand binding studies. In competition studies using [
3H]N-methylscopolamine ([
3H]NMS), gallamine displayed high affinity for the rat cardiac and guinea-pig uterine M
2 muscarinic receptors and for the atypical muscarinic receptor present in chicken heart. Gallamine displayed low affinity for rat glandular and human 1321 N1 astrocytoma cell M
3 receptors and also for the M
4 receptors of NG108-15 and PC12 cells. The compound displayed intermediate affinity for M
1 receptors of rat cortex labeled using [
3H]pirenzepine. The interaction of gallamine with the M
1 and M
2 receptors appeared to be competitive at the low concentrations required to determine affinity estimates. Thus, gallamine inhibited the binding of [
3H]pirenzepine to M
1 receptors and [
3H]NMS to M
2 receptors at concentrations that were 263- and 23-fold lower, respectively, than those required to decrease radioligand dissociation kinetics. Furthermore, gallamine, at a concentration that inhibited between 63 and 71% of specific radioligand binding, had no effect on the observed rate of association of the radioligand with either the M
1 or the M
2 receptor. At the M
3 glandular receptor, there was little separation between the concentrations of gallamine that produced inhibition of binding and those that decreased the association and dissociation rates of [
3H]NMS. It is therefore difficult to determine if the inhibition of binding seen in competition studies on the M
3 receptor was produced through a competitive or an allosteric mechanism. Despite its possible allosteric properties at the M
3 receptor, gallamine can be used to detect heterogeneity of muscarinic receptor subtypes in several tissues and therefore represents a useful tool for defining muscarinic receptor subtypes.