布罗莫普里德可以刺激人类心房中的5-HT4-色素受体
Lina Maria Rayo Abella1, Joachim Neumann2, Britt Hofmann3
1Institute for Pharmacology and Toxicology, Medical Faculty, Martin Luther University Halle-Wittenberg, Magdeburger Straße 4, D-06112, Halle (Saale), Germany.
Naunyn-Schmiedeberg's archives of pharmacology
|March 17, 2025
概括
布罗莫普里德作为人类心脏5-HT4-血清素受体的部分激动剂,影响心脏收缩力. 这一发现为布罗莫普里德提供了新的见解.
科学领域:
- 心血管药理学心血管药理学
- 血清素受体研究研究 血清素受体研究
背景情况:
- 布罗莫普里德是一种美托克洛普拉米德类似物,用于胃肠道疾病,主要是通过D2-多巴胺受体对抗作用.
- 布罗莫普里德与心脏色胺受体的潜在相互作用在很大程度上仍未被探索.
研究的目的:
- 为了调查布罗莫普里德是否作为人类心脏5-HT4-血清素受体的激动剂或对抗剂.
- 通过5-HT4-血清素受体相互作用来阐明布罗莫普里德对心脏收缩性的影响.
主要方法:
- 在孤立的人类心房准备剂 (HAP) 中测量收缩力 (FOC).
- 利用基因改造的小鼠模型 (5-HT4-TG) 过度表达人类心脏的5-HT4-血清素受体.
- 采用特定抗剂 (GR125487) 和固酶III抑制剂 (西洛斯塔米德) 来表征受体活性.
主要成果:
- 布罗莫普里德在5-HT4-TG小鼠的左心室制剂中显示出了FOC的度依赖的增加.
- 这种积极的内效应 (PIE) 被5-HT4-血清素受体对手GR125487.7阻止.
- 在人类心房制剂中,布罗莫普里德仅与西洛斯塔米德一起诱导PIE,而这种效果被GR125487抵制;此外,当血清素已经增加了FOC时,布罗莫普里德减少了FOC.
结论:
- 布罗莫普里德在人类心脏5-HT4-血清素受体上表现出部分激素活性.
- 这些发现表明,除了已知的多巴胺效应之外,布罗莫普里德还有一个新的作用机制.
相关概念视频
Drugs Affecting GI Tract Motility: Serotonin Receptor Agonists
201
Serotonin, a crucial neurotransmitter synthesized by enterochromaffin cells, plays a cardinal role in regulating gastrointestinal (GI) motility. With over 90% of the body's total serotonin in the GI tract, its influence on digestive processes is profound. Serotonin is swiftly released upon various stimuli, such as food boluses or certain drugs, triggering intrinsic sensory neurons in the myenteric plexus and extrinsic vagal and spinal sensory neurons. This leads to the activation of the...
201
Drugs Affecting GI Tract Motility: Dopamine Receptor Antagonists
231
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...
231
Direct-Acting Cholinergic Agonists: Pharmacological Actions
1.2K
Direct-acting cholinergic agonists exert their pharmacological actions by mimicking the effects of acetylcholine on postsynaptic muscarinic receptors to generate parasympathetic responses. These agents elicit a range of physiological responses, including cardiovascular effects. For example, activation of muscarinic receptors induces bradycardia, decreased cardiac output, reduced peripheral resistance, and consequent hypotension. In the eye, stimulation of M3 receptors leads to smooth muscle...
1.2K
Direct-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship
824
Cholinergic agonists or cholinomimetics mimic the action of acetylcholine to stimulate the parasympathetic nervous system. They are categorized into direct-acting and indirect-acting agents. The direct-acting cholinergic drugs induce the parasympathetic response by directly binding to the muscarinic or nicotine receptors. In comparison, the indirect-acting cholinergic drugs prevent acetylcholine hydrolysis, indirectly contributing to the extended parasympathetic response.
The direct-acting...
The direct-acting...
824
Adrenergic Agonists: Chemistry and Structure-Activity Relationship
2.5K
Adrenergic agonists' structure-activity relationship (SAR) determines their selectivity and efficacy. These agonists comprise a phenylethylamine moiety with an aromatic ring and an ethylamine side chain.
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of...
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of...
2.5K
Adrenergic Agonists: Indirect-Acting Agents
1.4K
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...
1.4K


