REGULATION OF IMIPRAMINE BINDING SITES IN RAT BRAIN

大鼠脑内丙咪嗪结合位点的调控

• 批准号: 4696401
• 负责人: M L BARBACCIA
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/4696401
• 关键词: antidepressants; axon; brain metabolism; chemical binding; desipramine; drug administration rate /duration; drug metabolism; drug tolerance; high performance liquid chromatography; human tissue; imipramine; molecular site; neural transmission; neuropharmacology; neurotransmitters; radiotracer; serotonin; serotonin inhibitor; synapses; tranquilizer

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.

选择性损伤5-HT轴突终末可显著降低5-HT轴突终末的表达。 标记的特异性高亲和力识别位点的数量 3 H-丙咪嗪，并防止α-肾上腺素能和 每日重复注射丙咪嗪引起的5-HT 2识别位点 (IMI)和去甲基丙咪嗪（DEMETHYMIMPRAMINE）。 此外，每天注射 IMI和CCl 2处理2-3周后，3 H-IMI结合最大值降低， 海马脑片摄取3 H-5-HT的Vmax增加。 这些发现 提示：1）3 H-IMI识别位点的相关药理作用 在介导慢性IMI引起的一些神经化学作用中， 治疗2）3 H-IMI识别对 位点调节5-HT再摄取的增益，从而调节5-HT 突触传递; 3）存在假定的内源性配体 （endacoid）的3 H-IMI结合位点，生理调节 3 H-5 HT再摄取。 一种非肽类热稳定性推定内分泌体， 以剂量依赖性方式抑制。 3 H-IMI结合和5 HT摄取非常 从大鼠脑中部分纯化。 HPLC保留时间和其他化学品 物理性质将其与5 HT和一系列吲哚-烷基 衍生物包括色托啉、5-羟基和5-甲氧基-色托啉。 大鼠脑的粗突触膜也含有特异性和高浓度的 3 H-米安色林的亲和受体位点，一种非典型抗抑郁药。 的 3 H-米安色林的接收位点似乎与5 HT 2不同 ~ 3 H-酮酶标记的识别位点：5-HT轴突终末损伤， 药理学治疗引发了对这两种药物的不同修改， 结合位点。 3 H-米安色林识别位点拟作为 涉及5 HT 2受体复合物的超分子结构 在调节血清能突触传递中的作用。