Binding affinity of sarpogrelate to 5-HT(2A) receptor ligand recognition sites in rat renal cortical and mesangial cells in culture.
We detected specific binding of 3H-ketanserin (0.6 nM) in rat renal cortical membrane preparations (4.70 +/- 0.57 fmol/mg protein) and mesangial cells (7.55 +/- 0.92 fmole/10(6) cells). Thus, the value in the renal cortical membrane corresponded to 15% of that in the cerebral cortical membranes (30.0 +/- 2.9 fmole/mg protein). The affinity of 3H-ketanserin binding displacement activities by sarpogrelate, a selective 5-HT2A receptor antagonist, in the renal cortical membrane (IC50; 0.448 +/- 0.061 microM) and mesangial cells (IC50; 0.656 +/- 0.187 microM) were almost 100-fold less than that in the cerebral cortical membrane (IC50; 4.62 +/- 1.02 nM). In the renal cortical membranes and mesangial cells, methysergide displaced a tiny fraction of 3H-ketanserin binding at concentrations up to 10 microM. These results did not explain the functional activity of 5-HT in the mesangial cells, and we conclude that specific 3H-ketanserin binding sites in the mesangial cells consisted of methysergide-resistant and non-serotonergic sites with low affinity for sarpogrelate.
Nishio
H
H
Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Hiroshima, Japan.
Yoshikawa
S
S
Morimoto
Y
Y
Chen
Z
Z
Nakata
Y
Y
D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D007650:Ketanserin / Q000378:metabolism; D007672:Kidney Cortex / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008566:Membranes / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D013386:Succinates / Q000378:metabolism*; D014316:Tritium
D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D013386:Succinates; D014316:Tritium; D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine; C064294:sarpogrelate; C003943:2,5-dimethoxy-4-bromoamphetamine; D007650:Ketanserin