氨基胺前期治疗通过一种阿里斯介导的机制使多巴胺诱导的D2/D3受体占用率减弱:在内化受损小鼠中进行的一项PET研究
Joseph B Mandeville1, Jonah Weigand-Whittier2, Hsiao-Ying Wey1
1Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
NeuroImage
|October 22, 2023
概括
激素挑战可以不准确地测量多巴胺D2/D3受体占用使用[11C]拉克洛普里德PET扫描. 野生类型小鼠的受体内化显著降低了痕迹剂的结合,与缺乏β-arrestin-2的淘汰小鼠不同.
科学领域:
- 神经科学是一个神经科学.
- 放射化学 放射化学是指辐射化学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 定子发射断层扫描 (PET) 放射标志物,如[11C]拉克洛普里德向多巴胺D2/D3受体.
- 对受体占用量的定量解释可能会被激素诱导的受体脱敏和内化所混.
- 了解这些动态受体变化对于准确的PET成像研究至关重要.
研究的目的:
- 调查阿雷斯介导的受体脱敏和内化对[11C]拉克洛普里德PET成像的影响.
- 为了比较野外类型 (WT) 和β-arrestin-2淘汰赛 (KO) 老鼠在安非他命挑战后的多巴胺D2/D3受体占用率.
- 阐明影响放射性追踪剂结合亲和力和PET解释的机制.
主要方法:
- 在未经药物治疗的WT和KO小鼠中使用了[11C]拉克洛普里德PET.
- 通过扫描内输注和3小时的预处理来调节多巴胺水平.
- 在不同的实验条件下评估了无线电配体-受体结合动力学和占用率.
主要成果:
- 在没有先前治疗的WT和KO小鼠中,安非他胺诱导的占用率相似.
- 在安非他命后3小时,WT小鼠的结合潜力比KO小鼠低15%.
- 接受器占用在KO小鼠中被保留,但在WT小鼠中被抑制了60%,表明功能性受体损失.
结论:
- 阿雷斯介导的受体脱敏化和内化显著影响PET [11C]拉克洛普里德占用率研究.
- 这些细胞机制可以导致在激素挑战范式中低估受体可用性.
- 这些发现强调了考虑受体动态对于精确的基于PET的神经递质系统成像的重要性.
更多相关视频
相关概念视频
01:21Drugs Affecting Neurotransmitter Release or Uptake
1.1K
Certain drugs can affect how neurotransmitters called catecholamines, are released or taken back up in the adrenergic neuron. They can have different effects on the body's sympathetic transmission. Reserpine, a natural compound found in the Rauwolfia shrub, blocks a transporter called vesicular monoamine transporter (VMAT), which leads to a buildup of catecholamines in the cell and reduces sympathetic transmission. Another drug called guanethidine works in multiple ways, including blocking...
1.1K
01:25Adrenergic Agonists: Indirect-Acting Agents
1.6K
Indirect-acting adrenergic agonists potentiate the effects of endogenous catecholamines through different mechanisms without directly binding to adrenoceptors.
One mechanism involves depleting stored catecholamines by displacing them from synaptic vesicles. These agents, known as "displacers," are transported into vesicles at the expense of noradrenaline. Examples include amphetamine and tyramine, which lack a catechol moiety, resulting in prolonged action, improved oral...
One mechanism involves depleting stored catecholamines by displacing them from synaptic vesicles. These agents, known as "displacers," are transported into vesicles at the expense of noradrenaline. Examples include amphetamine and tyramine, which lack a catechol moiety, resulting in prolonged action, improved oral...
1.6K
01:29Drugs Affecting Neurotransmitter Synthesis
1.4K
Drugs affecting neurotransmitter synthesis can impact the adrenergic neuron and the synthesis of neurotransmitters. For example, α-methyltyrosine and carbidopa target specific enzymes involved in catecholamine synthesis. α-methyltyrosine inhibits the enzyme tyrosine hydroxylase, which converts tyrosine into dopamine. By blocking this enzyme, α-methyltyrosine reduces dopamine production and other catecholamines. Carbidopa, on the other hand, inhibits the enzyme dopa decarboxylase,...
1.4K
01:21Antipsychotic Drugs: Typical and Atypical Agents
223
Antipsychotic drugs are classified into first-generation (typical) drugs including phenothiazines; and second-generation (atypical) drugs. Chlorpromazine hydrochloride (Thorazine), a phenothiazine derivative, broadly impacts the central, autonomic, and endocrine systems. This drug, along with typical agents like haloperidol (Haldol), primarily works by antagonizing D2 receptors, thus reducing dopaminergic neurotransmission. However, typical antipsychotics can cause side effects such as sedation...
223
01:26Neurochemical Transmission: Sites of Drug Action
2.4K
Neurochemical transmission, the conduction of electrical impulses between neurons mediated by neurotransmitters, plays a vital role in various physiological processes. Autonomic drugs exert their effects by modulating neurotransmission within the autonomic nervous system. For instance, drugs such as hemicholinium block the precursor uptake necessary for synthesizing acetylcholine, an essential autonomic neurotransmitter. Following synthesis, neurotransmitters are stored in vesicles. Metyrosine...
2.4K
01:28Drugs Affecting GI Tract Motility: Dopamine Receptor Antagonists
350
Prokinetic agents are specialized medications that stimulate gastrointestinal (GI) motility, promoting food movement through the GI tract. Dopamine, an inhibitory neurotransmitter, plays a significant role in this process, reducing GI motility and indirectly controlling the speed of digestion. Dopamine receptor antagonists, such as metoclopramide and domperidone, offer a unique advantage as prokinetic agents. By blocking the dopamine receptors, these drugs increase GI motility, improving food...
350