Pharmacological activity of NF-κB decoy (II). Effect of NF-κB decoy on Colon26-induced cachexia in mice.

We previously reported molecular cloning of human 5-HT3 receptors (MoL PharmacaL 1995, 48, 407-416).Additionally, we isolated eDNA of human 5-HT4 receptor.The genomic sequence of human 5-HT 4 receptor was already reported by another group (W094/1 4957).In the present studies, the property of [ 3 H]ramosetron(YM060) binding to cloned human 5-HT3 receptors and eHJGRII3808 binding to cloned human 5-HT 4 receptors was investigated.The affinity of various compounds for both receptors was determined.To obtain membrane homogenates for binding study, COS-I cells were transfected with human 5-HT3 or 5-HT4 receptor gene.eHJramosetron bound to cloned human 5-HT3 receptors with high affinity (1<.!=0.16 nM, Bm,.=412 fmol/mg protrin).eHJGRII3808 bound to cloned human 5-HT4 receptors with high affinity (1<.!=0.1 nM, Bm ax=270 fmol/mg protein).The affinity rank order of compounds for human 5-HT3 receptors was as follows: ramosetron > zacopride > tropisetron > renzapride > 5-HT > GR1 13808 > cisapride > 2-meyhyl-5-HT and for human 5-HT4 receptors was as follows: GR113808 > cisapride > tropisetron > 5-HT > renzapride > 5-methoxytryptamine > ramosetron.Other 5-HT receptor agonists and antagonists, such as 8-0H-DPAT, methysergide and ketanserin did not inhibit specific binding for both receptors.