REGULATION OF IMIPRAMINE BINDING SITES IN RAT BRAIN

选择性损毁5-羟色胺轴突终末可显著降低 标记的特定高亲和力识别位点的数量 ~3H-丙咪嗪抑制α-肾上腺素能和肾上腺素能的下调 丙咪嗪重复注射引起的5-HT2识别位点 (IMI)和去甲基米帕明(DMI)。此外，在每天注射 IMI和DMI 2-3周后，~3H-IMI结合的最大值降低，而 海马片摄取~(3 H)-5-羟色胺的Vmax增加。这些发现 提示：1)~3H-IMI识别位点具有相关的药理学作用 在介导慢性IMI引起的某些神经化学效应中的作用 处理2)~3H-IMI识别的可能生理作用 调节5-羟色胺再摄取从而调节5-羟色胺再摄取增益的部位 突触传递；3)假定存在内源性配体 (Endacid)为~3H-IMI结合部位，它生理上调节 ~3H-5-羟色胺再摄取。一种非肽类耐热内酯类化合物 以剂量依赖的方式抑制。~3H-IMI结合与5-羟色胺摄取 部分从大鼠脑中提纯。高效液相保留时间及其他化学物质 物理性质使其有别于5-羟色胺和一系列吲哚烷基 异构体包括色氨酸、5-羟基和5-甲氧基-色氨酸。 大鼠脑内的粗突触膜也含有特异性高的 非典型抗抑郁药~3H-Mianserin的亲和受体部位。这个 ~3H-Mianserin的接受部位似乎与5HT2不同 ~3H-Ketausei标记的识别位点：5-羟色胺轴突终末损伤和 药物治疗对两者有不同的修饰作用 结合部位。~3H-Mianserin识别位点被提议作为 参与了5HT2受体复合体的超分子组织 在血清能突触传递的调制中。

A selective lesion of the 5-HT axon terminals significantly decreases the number of specific high affinity recognition sites labelled by 3H-imipramine and prevents the down regulation of Alpha-adrenergic and of 5-HT2 recognition sites elicited by repeated daily injections of imipramine (IMI) and desmethylimipramine (DMI). Moreover after daily injections of IMI and DMI for 2-3 weeks the max of 3H-IMI binding is decreased while the Vmax of 3H-5-HT uptake in hippocampus slices is increased. These findings suggest: 1) a relevant pharmacological role of the 3H-IMI recognition site in mediating some of the neurochemical effects elicited by chronic IMI treatment 2) a possible physiological role of the 3H-IMI recognition on sites in modulating the gain of the 5HT reuptake and thereby the 5HT synaptic transmission; 3) the existence of a putative endogenous ligand (endacoid) for the 3H-IMI binding site which physiological modulates the 3H-5HT reuptake. A nonpeptide thermostable putative endacoid which inhibits in a dose-dependent manner. 3H-IMI binding and 5HT uptake very partially purified from rat brain. HPLC retention time and other chemical physical properties differentiate it from 5HT and a series of indole-alkyl devivatives including tryptoline, 5-hydroxy and 5-methoxy-tryptoline. Crude synaptic membrane from rat brain contain also specific and high affinity reception sites for 3H-Mianserin an atypical antidepressant. The 3H-Mianserin reception sites appear to be different from the 5HT2 recognition sites labelled by 3H-Ketausei: 5HT axon terminals lesion and pharmacological treatments elicita different modifications upon the two binding sites. The 3H-Mianserin recognition site is proposed to be part of the supramolecular organization of the 5HT2 receptor complex are involved in the modulation of the seronergic synaptic transmission.