Eisenhofer G
Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, Building 10, Room 6N 252, National Institutes of Health, 10 Center Drive, MSC 1620, Bethesda, MD 20892-1620, USA.
Pharmacol Ther. 2001 Jul;91(1):35-62. doi: 10.1016/s0163-7258(01)00144-9.
Catecholamines are translocated across plasma membranes by transporters that belong to two large families with mainly neuronal or extraneuronal locations. In mammals, neuronal uptake of catecholamines involves the dopamine transporter (DAT) at dopaminergic neurons and the norepinephrine transporter (NET) at noradrenergic neurons. Extraneuronal uptake of catecholamines is mediated by organic cation transporters (OCTs), including the classic corticosterone-sensitive extraneuronal monoamine transporter. Catecholamine transporters function as part of uptake and metabolizing systems primarily responsible for inactivation of transmitter released by neurons. Additionally, the neuronal catecholamine transporters, recycle catecholamines for rerelease, thereby reducing requirements for transmitter synthesis. In a broader sense, catecholamine transporters function as part of integrated systems where catecholamine synthesis, release, uptake, and metabolism are regulated in a coordinated fashion in response to the demands placed on the system. Location is also important to function. Neuronal transporters are essential for rapid termination of the signal in neuronal-effector organ transmission, whereas non-neuronal transporters are more important for limiting the spread of the signal and for clearance of catecholamines from the bloodstream. Besides their presynaptic locations, NET and DAT are also present at several extraneuronal locations, including syncytiotrophoblasts of the placenta and endothelial cells of the lung (NET), stomach and pancreas (DAT). The extraneuronal monoamine transporter shows a broad tissue distribution, whereas the other two non-neuronal catecholamine transporters (OCT1 and OCT2) are mainly localized to the liver, kidney, and intestine. Altered function of peripheral catecholamine transporters may be involved in disturbances of the autonomic nervous system, such as occurs in congestive heart failure and hypernoradrenergic hypertension. Peripheral catecholamine transporters provide important targets for clinical imaging of sympathetic nerves and diagnostic localization and treatment of neuroendocrine tumors, such as neuroblastomas and pheochromocytomas.
儿茶酚胺通过转运体跨质膜转运，这些转运体属于两个主要定位于神经元或非神经元的大家族。在哺乳动物中，儿茶酚胺的神经元摄取涉及多巴胺能神经元上的多巴胺转运体（DAT）和去甲肾上腺素能神经元上的去甲肾上腺素转运体（NET）。儿茶酚胺的非神经元摄取由有机阳离子转运体（OCTs）介导，包括经典的皮质酮敏感的非神经元单胺转运体。儿茶酚胺转运体作为摄取和代谢系统的一部分发挥作用，主要负责使神经元释放的递质失活。此外，神经元儿茶酚胺转运体回收儿茶酚胺以便再次释放，从而减少对递质合成的需求。从更广泛的意义上讲，儿茶酚胺转运体作为整合系统的一部分发挥作用，在该系统中，儿茶酚胺的合成、释放、摄取和代谢根据系统需求以协调的方式进行调节。位置对功能也很重要。神经元转运体对于神经元 - 效应器器官传递中信号的快速终止至关重要，而非神经元转运体对于限制信号扩散以及从血液中清除儿茶酚胺更为重要。除了它们的突触前位置外，NET和DAT也存在于几个非神经元位置，包括胎盘的合体滋养层细胞和肺（NET）、胃和胰腺（DAT）的内皮细胞。非神经元单胺转运体显示出广泛的组织分布，而其他两种非神经元儿茶酚胺转运体（OCT1和OCT2）主要定位于肝脏、肾脏和肠道。外周儿茶酚胺转运体功能的改变可能参与自主神经系统的紊乱，如在充血性心力衰竭和高去甲肾上腺素能性高血压中发生的情况。外周儿茶酚胺转运体为交感神经的临床成像以及神经母细胞瘤和嗜铬细胞瘤等神经内分泌肿瘤的诊断定位和治疗提供了重要靶点。
