Binding affinity of sarpogrelate to 5-HT2A receptor ligand recognition sites in rat renal cortical and mesangial cells in culture

We detected specific binding of H-3-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 H-3-ketanserin binding displacement activities by sarpogrelate, a selective 5-HT2A receptor antagonist, in the renal cortical membrane. (IC50; 0.448 +/- 0.061 mu M) and mesangial cells (IC50; 0.656 +/- 0.187 mu M) 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 mu M. These results did not explain the functional activity of 5-HT in the mesangial cells, and we conclude that specific H-3-ketanserin binding sites in the mesangial cells consisted of methysergide-resistant and non-serotonergic sites with low affinity for sarpogrelate. (C) 1999 Elsevier Science Inc. All rights reserved.