多巴胺通过胆固醇依赖和独立的通路调节结肠质细胞衍生的神经营养因子分泌
Xiao-Li Zhang1, Qi Sun1, Zhu-Sheng Quan1
1Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
British journal of pharmacology
|August 24, 2023
概括
多巴胺差异调节结肠GDNF分泌. 低多巴胺水平通过D1受体促进GDNF释放,而高水平通过D2受体抑制它,影响肠道平衡.
科学领域:
- 神经胃肠病学 神经胃肠病学
- 肠道生理学肠道生理学
- 神经药理学神经药理学
背景情况:
- 质细胞衍生神经营养因子 (GDNF) 对于维持肠道平衡至关重要.
- 已知多巴胺可以刺激星球细胞的GDNF释放.
- 调节多巴胺对结肠GDNF分泌的控制的精确机制尚未完全阐明.
研究的目的:
- 研究多巴胺在调节结肠GDNF分泌中的双重作用.
- 为了确定涉及本条例的特定多巴胺受体亚型和细胞类型.
- 了解对肠道功能的影响和潜在的治疗点.
主要方法:
- 使用了D1受体淘汰赛小鼠,AAV9-shD2R治疗的小鼠,6-OHDA治疗的老鼠和初级肠质细胞 (EGC) 培养物.
- 在结肠组织和EGC培养物中测量了GDNF和乙胆 (ACh) 水平.
- 采用受体激动剂,抗剂和成像来阐明信号通路.
主要成果:
- 低多巴胺度通过胆固醇神经元上的D1受体刺激了结肠GDNF分泌,增加了ACH释放.
- 高度的多巴胺抑制了EGC和/或胆固醇神经元上的D2受体通过GDNF分泌,减少了ACH释放.
- 多巴胺的作用依赖于度,并通过特定的受体相互作用进行介导.
结论:
- 多巴胺对基于度的结肠GDNF分泌产生相反的影响,通过不同的受体通路起作用.
- D1受体激活促进GDNF释放,支持肠道功能,而D2受体激活则抑制了它.
- 这些发现凸显了结肠中GDNF的复杂多巴胺基调节机制,对胃肠道疾病有影响.
相关概念视频
01:23Cholinergic Neurons: Neurotransmission
3.1K
Cholinergic neurotransmission involves the synthesis and the release of acetylcholine (ACh) in order to transmit nerve impulses across the synapse. The process begins with the synthesis of acetyl CoA, a precursor for ACh, from ATP, acetate, and coenzyme A in the mitochondria. Choline, another vital precursor, is transported inside the neuron through choline transporters, including high-affinity choline transporter CHT1, low-affinity choline transporter CTL1, and lower-affinity choline...
3.1K
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
01:37Neural Regulation
39.5K
Digestion begins with a cephalic phase that prepares the digestive system to receive food. When our brain processes visual or olfactory information about food, it triggers impulses in the cranial nerves innervating the salivary glands and stomach to prepare for food.
39.5K
01:28Drugs Affecting GI Tract Motility: Dopamine Receptor Antagonists
392
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...
392
01:11Enteric Nervous System: Regulation of GI Motor Activity
454
The Enteric Nervous System (ENS) plays a pivotal role in regulating gastrointestinal or GI motor activity. This complex network of nerves, deeply embedded within the gut wall, responds to changes in the gut environment and receives input from both the autonomic nervous system and the central nervous system. By doing so, the ENS operates various programs tailored to the body's nutritional status and needs.
During periods of fasting, the ENS initiates the migrating myoelectric complex, a...
During periods of fasting, the ENS initiates the migrating myoelectric complex, a...
454
01:23Drugs Acting on Autonomic Ganglia: Stimulants
1.4K
Ganglionic stimulants activate NM nicotinic receptors in autonomic ganglia, falling into two categories: nicotine mimetics [e.g., lobeline, dimethylpiperazine, tetramethylammonium] and muscarinic receptor agonists [e.g., muscarine, methacholine]. The first category's action is rapid and blocked by nicotinic receptor antagonists, while the second category's action is delayed and blocked by atropine-like agents. Nicotine, an alkaloid, affects the heart rate by stimulating...
1.4K