使用[125I]-DOI（一种选择性拟精神病放射性配体）对大鼠脑中5HT2受体进行放射自显影定位。

Autoradiographic localization of 5HT2 receptors in rat brain using [125I]-DOI, a selective psychotomimetic radioligand.

Nazarali A J, McKenna D J, Saavedra J M

Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland.

Prog Neuropsychopharmacol Biol Psychiatry. 1989;13(3-4):573-81. doi: 10.1016/0278-5846(89)90149-8.

Abstract

Binding sites for the R and S enantiomers of the 5HT2 agonist DOI (2,5-dimethoxy-4-iodophenylisopropylamine) were identified in rat brain using quantitative in-vitro autoradiography and compared with [125I]-LSD binding. 2. In most regions of the brain, binding density of the less active isomer [125I]S-DOI was 15 to 85% of that exhibited by the active [125I]R-DOI isomer. 3. Cortical membrane preparations exhibited two binding sites, of the enantiomers with high (KdH) and low (KdL) affinity constants of 1.2 +/- 0.02 nM and 29 +/- 7 nM for the [125I]R-DOI and 2.1 +/- 0.2 nM and 18 +/- 4 nM for [125I]S-DOI respectively. The respective high (BmaxH) and low (BmaxL) binding densities were 92 +/- 10 and 536 +/- 164 fmol/mg protein for the [125I]R-DOI and 67 +/- 19 and 245 +/- 60 fmol/mg protein for [125I]S-DOI. 4. Our results correlate with regional distribution of 5HT2 receptors reported in previous studies and indicate that DOI and its congeners have potential clinical applications for the in-vivo localization of 5HT2 receptors.

摘要

利用定量体外放射自显影技术在大鼠脑中鉴定了5-羟色胺2（5HT2）激动剂DOI（2,5-二甲氧基-4-碘苯异丙胺）的R型和S型对映体的结合位点，并与[125I]-麦角酸二乙胺（LSD）结合进行了比较。2. 在大脑的大多数区域，活性较低的异构体[125I]S-DOI的结合密度是活性[125I]R-DOI异构体的15%至85%。3. 皮质膜制剂显示出两个结合位点，对于[125I]R-DOI，对映体的高亲和力常数（KdH）和低亲和力常数（KdL）分别为1.2±0.02 nM和29±7 nM，对于[125I]S-DOI分别为2.1±0.2 nM和18±4 nM。[125I]R-DOI各自的高结合密度（BmaxH）和低结合密度（BmaxL）分别为92±10和536±164 fmol/mg蛋白，[125I]S-DOI的分别为67±19和245±60 fmol/mg蛋白。4. 我们的结果与先前研究中报道的5HT2受体的区域分布相关，并表明DOI及其同系物在5HT2受体的体内定位方面具有潜在的临床应用。