Alexander B S, Wood M D
Wyeth Research (UK), Taplow, Maidenhead, Berkshire.
J Pharm Pharmacol. 1988 Dec;40(12):888-91. doi: 10.1111/j.2042-7158.1988.tb06296.x.
The binding of [3H]8-hydroxy-2-(di-N-propylamino)-tetralin ([ 3H]8-OH-DPAT) to rat hippocampal and striatal membranes has been compared. In the hippocampus, low concentrations of [3H]8-OH-DPAT bound to a single, high affinity site which was sensitive to inhibition by spiperone, buspirone and ergotamine but not by mianserin, quipazine or (-)-propranolol. This is consistent with a selective labeling of the 5-HT1A receptor. In the striatum, [3H]8-OH-DPAT bound to two sites with high and low affinity (KD's 1.18 and 109 nM). The high affinity component was blocked by low concentrations of buspirone, spiperone and ergotamine. The low affinity component was blocked only by high concentrations of buspirone and spiperone, and was not displaced by ergotamine at concentrations up to 1 microM. The ergotamine-resistant component of striatal [3H]8-OH-DPAT binding was blocked by low concentrations of the 5-HT uptake inhibitors fluvoxamine and paroxetine, and by relatively low concentrations of 5-HT itself. Thus [3H]8-OH-DPAT labels the 5-HT transporter in the rat striatum. Unlike [3H]imipramine binding, the binding of [3H]8-OH-DPAT to the 5-HT transporter was independent of external sodium ions. It is therefore suggested that 8-OH-DPAT acts as substrate for the 5-HT transporter and labels the 5-HT recognition site of the transporter complex.
已对[3H]8-羟基-2-(二-N-丙基氨基)-四氢萘([3H]8-OH-DPAT)与大鼠海马体和纹状体膜的结合情况进行了比较。在海马体中，低浓度的[3H]8-OH-DPAT与一个单一的高亲和力位点结合，该位点对螺哌隆、丁螺环酮和麦角胺的抑制敏感，但对米安色林、喹哌嗪或(-)-普萘洛尔不敏感。这与5-HT1A受体的选择性标记一致。在纹状体中，[3H]8-OH-DPAT与两个具有高亲和力和低亲和力的位点结合（解离常数分别为1.18和109 nM）。高亲和力成分被低浓度的丁螺环酮、螺哌隆和麦角胺阻断。低亲和力成分仅被高浓度的丁螺环酮和螺哌隆阻断，且在浓度高达1 microM时不受麦角胺的置换。纹状体[3H]8-OH-DPAT结合的麦角胺抗性成分被低浓度的5-羟色胺摄取抑制剂氟伏沙明和帕罗西汀以及相对低浓度的5-羟色胺本身阻断。因此，[3H]8-OH-DPAT标记了大鼠纹状体中的5-羟色胺转运体。与[3H]丙咪嗪结合不同，[3H]8-OH-DPAT与5-羟色胺转运体的结合不依赖于细胞外钠离子。因此，有人提出8-OH-DPAT作为5-羟色胺转运体的底物，并标记转运体复合物的5-羟色胺识别位点。
