Nishio H, Yoshikawa S, Morimoto Y, Chen Z, Nakata Y
Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Hiroshima, Japan.
Gen Pharmacol. 1999 Jul;33(1):51-7. doi: 10.1016/s0306-3623(98)00266-3.
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.
我们在大鼠肾皮质膜制剂（4.70±0.57 fmol/mg蛋白质）和系膜细胞（7.55±0.92 fmol/10⁶细胞）中检测到³H-酮色林（0.6 nM）的特异性结合。因此，肾皮质膜中的值相当于大脑皮质膜中值（30.0±2.9 fmol/mg蛋白质）的15%。选择性5-HT₂A受体拮抗剂沙芦普列特对肾皮质膜（IC₅₀；0.448±0.061 μM）和系膜细胞（IC₅₀；0.656±0.187 μM）中³H-酮色林结合置换活性的亲和力比大脑皮质膜（IC₅₀；4.62±1.02 nM）低近100倍。在肾皮质膜和系膜细胞中，甲基麦角新碱在浓度高达10 μM时仅置换了一小部分³H-酮色林结合。这些结果无法解释5-HT在系膜细胞中的功能活性，我们得出结论，系膜细胞中的特异性³H-酮色林结合位点由对沙芦普列特亲和力低的甲基麦角新碱抗性和非5-羟色胺能位点组成。
