Comparative study of [3H]ramosetron and [3H]granisetron binding in the cloned human 5-hydroxytryptamine3 receptors.
Characteristics of the binding of [3H]ramosetron to cloned human 5-hydroxytryptamine3 (5-HT3) receptors were investigated and directly compared to those of [3H]granisetron binding. Saturation studies revealed that [3H]ramosetron labeled more sites with high affinity (Kd=0.15+/-0.01 nM, Bmax =653 +/- 30 fmol/mg protein) than [3H]granisetron (Kd=1.17+/-0.25 nM, Bmax=427+/-43 fmol/mg protein). Kinetic studies revealed that dissociation of [3H]ramosetron was slower than that of [3H]granisetron. These results suggest that ramosetron is a highly potent 5-HT3-receptor antagonist.
Akuzawa
S
S
Neuroscience Research, Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan.
Ito
H
H
Yamaguchi
T
T
D000818:Animals; D001562:Benzimidazoles / Q000378:metabolism*; D001667:Binding, Competitive; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism; D017829:Granisetron / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D011985:Receptors, Serotonin / Q000235:genetics / Q000378:metabolism*; D044406:Receptors, Serotonin, 5-HT3; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014316:Tritium
D001562:Benzimidazoles; D017829:Granisetron; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D011993:Recombinant Fusion Proteins; D014316:Tritium; C071315:ramosetron