[High affinity binding of Y-25130 for serotonin 3 receptor].
The binding of Y-25130 on serotonin 3 (5-HT3) receptors was evaluated by examining its effect on 3H-BRL 43694 (3H-granisetron) binding to rat cerebral cortex membranes in comparison with those of granisetron, ondansetron and metoclopramide. Y-25130, granisetron, ondansetron, metoclopramide, 5-HT and 2-methyl-5-HT displaced the specific binding of 3H-granisetron to the synaptosomal membranes in a concentration-dependent manner. The rank order of potency for inhibition of 3H-granisetron binding by the test compounds was Y-25130 not equal to granisetron greater than ondansetron much greater than 2-methyl-5-HT not equal to 5-HT not equal to metoclopramide. To determine the manner of interaction between Y-25130 and 5-HT3 receptors, Scatchard analysis of 3H-granisetron specific binding to the membranes of the cerebral cortex in the absence or presence of various concentrations of Y-25130 was performed. It was indicated that Y-25130 exerted a typical competitive-type inhibition of 3H-granisetron binding. The present study indicates that Y-25130 binds competitively to 5-HT3 receptors with high affinity.
Sakamori
M
M
Research Laboratories, Yoshitomi Pharmaceutical Industries, Ltd., Fukuoka, Japan.
Takehara
S
S
Setoguchi
M
M
D000818:Animals; D000932:Antiemetics / Q000378:metabolism*; D001667:Binding, Competitive; D001643:Bridged Bicyclo Compounds / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002540:Cerebral Cortex / Q000378:metabolism; D017829:Granisetron; D066298:In Vitro Techniques; D007191:Indazoles / Q000378:metabolism; D008297:Male; D017294:Ondansetron / Q000378:metabolism; D010078:Oxazines / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000378:metabolism*; D013570:Synaptic Membranes / Q000378:metabolism
D000932:Antiemetics; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D017829:Granisetron; D007191:Indazoles; D017294:Ondansetron; D010078:Oxazines; D011985:Receptors, Serotonin; C070671:azasetron