[Cisapride, a gastroprokinetic agent, binds to 5-HT4 receptors].
The affinity of cisapride for 5-HT4 receptors was investigated in comparison with those of other 5-HT4 receptor agonists and antagonists, such as 5-HT, 5-MeOT, mosapride, zacopride, metoclopramide, BIMU8, GR113808, SDZ 205-557 and ICS 205-930. Cisapride and the other compounds dose-dependently inhibited specific 3H-GR113808 binding to 5-HT4 receptors in guinea pig striatal membranes, and complete inhibition of specific 3H-GR113808 binding was achieved at the high concentrations of these compounds. Cisapride was 1.9-, 7.3-, 4.3-, 11- and 26-fold more potent than 5-HT, 5-MeOT, mosapride, zacopride and metoclopramide, respectively, in competing for 5-HT4 receptors. To determine the manner of interaction between cisapride and 5-HT4 receptors, Scatchard analysis of 3H-GR113808 specific binding to striatal membranes was performed. Cisapride increased the Kd value of 3H-GR113808 in striatal membranes in a dose-dependent manner without any influence on the binding density (Bmax) of 3H-GR113808. These findings indicate that cisapride binds to 5-HT4 receptors competing with 3H-GR113808 in guinea pig striatal membranes.
Katayama
K
K
Research Laboratories, Yoshitomi Pharmaceutical Industries, Ltd., Fukuoka, Japan.
Morio
Y
Y
Haga
K
K
Fukuda
T
T
D000818:Animals; D001667:Binding, Competitive; D020117:Cisapride; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D010880:Piperidines / Q000378:metabolism* / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000378:metabolism
D010880:Piperidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D020117:Cisapride