Malgouris C, Flamand F, Doble A
Rhône-Poulenc Rorer, Centre de Recherche de Vitry-Alfortville, Vitry-sur-Seine, France.
Eur J Pharmacol. 1993 Mar 16;233(1):37-45. doi: 10.1016/0014-2999(93)90346-j.
The binding properties and localization of [3H]RP 62203, a novel ligand for 5-HT2 receptors, were investigated on rat brain sections. The specific binding of this 5-HT2 receptor antagonist was reversible and could be displaced by ritanserin (1 microM). Saturation experiments revealed a single class of binding sites with a KD of 0.128 +/- 0.018 nM and a Bmax of 1.67 +/- 0.06 pmol/mg protein. Pharmacological specificity was demonstrated by the potency order of displacing agents: RP 62203 > ritanserin > spiperone > methysergide > mianserin > pipamperone > cinanserin > 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Quantitative autoradiography showed a heterogeneous distribution of [3H]RP 62203 binding sites, with the highest densities in the frontal, parietal and auditory cortices (layer IV), claustrum and olfactory bulb. Binding densities in the occipital cortex, caudate putamen and thalamic nuclei were moderate, whereas the hippocampus and substantia nigra displayed a very low density of binding sites. The cerebellar cortex appeared almost devoid of [3H]RP 62203 binding sites. The anatomical distribution of binding sites demonstrated that [3H]RP 62203 essentially bound only to rat brain regions known to contain 5-HT2 receptors. This ligand could thus be a useful tool to visualize 5-HT2 receptors.
在大鼠脑切片上研究了新型5-羟色胺2（5-HT2）受体配体[3H]RP 62203的结合特性和定位。这种5-HT2受体拮抗剂的特异性结合是可逆的，可被利坦色林（1 microM）取代。饱和实验显示存在一类结合位点，解离常数（KD）为0.128±0.018 nM，最大结合容量（Bmax）为1.67±0.06 pmol/mg蛋白质。通过取代剂的效价顺序证明了药理学特异性：RP 62203＞利坦色林＞螺哌隆＞甲基麦角新碱＞米安色林＞匹泮哌隆＞西那色林＞1-（2,5-二甲氧基-4-碘苯基）-2-氨基丙烷（DOI）。定量放射自显影显示[3H]RP 62203结合位点分布不均一，在额叶、顶叶和听觉皮层（IV层）、屏状核和嗅球中密度最高。枕叶皮层、尾状壳核和丘脑核中的结合密度中等，而海马体和黑质的结合位点密度非常低。小脑皮层几乎没有[3H]RP 62203结合位点。结合位点的解剖分布表明，[3H]RP 62203基本上只与已知含有5-HT2受体的大鼠脑区结合。因此，这种配体可能是可视化5-HT2受体的有用工具。
