针对阴离子-化物共载体生理学的化合物的药理学
Eric Delpire1, Andrew S Terker2, Kenneth B Gagnon3
1Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, TN, USA. eric.delpire@vanderbilt.edu.
Handbook of experimental pharmacology
|August 10, 2023
概括
溶解物载体家族12 (SLC12) 载体,包括Na-Cl共载体 (NCC) 和Na-K-2Cl共载体-2 (NKCC2),对脏盐的再吸收至关重要,并且是利尿剂的目标. 新的药理学药剂正在加强对这些载体的研究.
科学领域:
- 身体生理学 身体生理学
- 药理学 药理学是指药理学的学科.
- 分子生物学分子生物学
背景情况:
- 溶液载体家族12 (SLC12) 载体促进无机 (Na+,K+) 和 (Cl-) 通过细胞膜的电子中性运输.
- 关键成员NKCC2和NCC对于脏盐的再吸收至关重要,形成广泛使用的利尿剂 (如循环和化利尿剂) 的标.
- 新兴的研究突出显示了bumetanide在神经发育障碍中的潜力,扩大了SLC12载体的治疗范围.
研究的目的:
- 审查SLC12载体在细胞功能和疾病中的关键作用.
- 讨论SLC12载体药理上的进展,包括新型强效抑制剂和刺激剂.
- 要突出冷电子显微镜对理解载体-连接体相互作用的影响.
主要方法:
- 对SLC12载体,它们的生理作用和药理向的现有文献的审查.
- 对详细介绍开发用于SLC12载体的新型药理学药物的研究进行分析.
- 检查最近的冷电子显微镜研究,阐明药物转运体结合部位和机制.
主要成果:
- 识别K-Cl携带载体的强效抑制剂和潜在刺激剂,超越现有的药物,如furosemide.
- 证明SLC12载体在各种组织中的广泛生理重要性.
- 进步了解利尿剂作用的分子机制和潜在的新疗法应用.
结论:
- SLC12转运体对于维持生理平衡至关重要,并代表了重要的治疗点.
- 药理学研究已经产生了SLC12载体的高强度和选择性调节器,提供了新的研究工具和治疗途径.
- 电子显微镜正在彻底改变我们对药物如何与SLC12载体在分子水平上相互作用的理解.
相关概念视频
01:14Active Transport
757
Active transport is a critical biological process that allows cells to move solutes against an electrochemical gradient. This process requires direct energy input and is characterized by its selectivity, saturability, and susceptibility to competitive inhibition.
Primary active transporters, like Na+, K+ and -ATPase, directly utilize ATP to move ions across the membrane. These transporters play significant roles in various physiological processes. For instance, Na+, K+ and -ATPase maintain...
Primary active transporters, like Na+, K+ and -ATPase, directly utilize ATP to move ions across the membrane. These transporters play significant roles in various physiological processes. For instance, Na+, K+ and -ATPase maintain...
757
01:17Pore Transport and Ion-Pair Transport
513
Pore transport and ion-pair formation are critical mechanisms for the absorption and distribution of drugs in the body.
Pore transport, also known as convective transport, is a process where small molecules like urea, water, and sugars rapidly cross cell membranes as though there were channels or pores in the membrane. Although direct microscopic evidence is limited but the concept of pores or channels is widely accepted based on physiological evidence. Despite the lack of direct...
Pore transport, also known as convective transport, is a process where small molecules like urea, water, and sugars rapidly cross cell membranes as though there were channels or pores in the membrane. Although direct microscopic evidence is limited but the concept of pores or channels is widely accepted based on physiological evidence. Despite the lack of direct...
513
01:32Secondary Active Transport
7.2K
One example of how cells use the energy contained in electrochemical gradients is demonstrated by glucose transport into cells. The ion vital to this process is sodium (Na+), which is typically present in higher concentrations extracellularly than in the cytosol. Such a concentration difference is due, in part, to the action of an enzyme "pump" embedded in the cellular membrane that actively expels Na+ from a cell. Importantly, as this pump contributes to the high concentration of...
7.2K
01:31Membrane Transporters
11.6K
Transporters are essential membrane transport proteins with functions related to cell nutrition, homeostasis, communication, etc. Approximately 7% of all genes in the human genome code for transporters or transporter-related proteins.
Transporters are mainly composed of alpha-helices, built from bundles of ten or more helices traversing the plasma membrane. The solute-binding sites are located midway, where some of the helices are broken or distorted, making space for the binding site through...
Transporters are mainly composed of alpha-helices, built from bundles of ten or more helices traversing the plasma membrane. The solute-binding sites are located midway, where some of the helices are broken or distorted, making space for the binding site through...
11.6K
01:06Carrier-Mediated Transport
469
Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
469
01:31ABC Transporters: Exporter
4.4K
ATP-binding cassette or ABC transporter is the largest superfamily of integral membrane proteins. The transporters have transmembrane-binding domains (TMDs) and nucleotide-binding domains (NBDs). The TMDs are specific to their substrates, whereas the NBDs are similar to engines that complete ATP hydrolysis to complete the substrate transport. They can be full transporters consisting of two TMDs and NBDs, half transporters with one TMD and NBD, while some encoded with a single TMD or NBD are...
4.4K