Raidoo D M, Bhoola K D
Department of Physiology, Faculty of Medicine, University of Natal, Durban, South Africa.
Pharmacol Ther. 1998 Aug;79(2):105-27. doi: 10.1016/s0163-7258(98)00011-4.
The nervous system and peripheral tissues in mammals contain a large number of biologically active peptides and proteases that function as neurotransmitters or neuromodulators in the nervous system, as hormones or cellular mediators in peripheral tissue, and play a role in human neurological diseases. The existence and possible functional relevance of bradykinin and kallidin (the peptides), kallikreins (the proteolytic enzymes), and kininases (the peptidases) in neurophysiology and neuropathological states are discussed in this review. Tissue kallikrein, the major cellular kinin-generating enzyme, has been localised in various areas of the mammalian brain. Functionally, it may assist also in the normal turnover of brain proteins and the processing of peptide-hormones, neurotransmitters, and some of the nerve growth factors that are essential for normal neuronal function and synaptic transmission. A specific class of kininases, peptidases responsible for the rapid degradation of kinins, is considered to be identical to enkephalinase A. Additionally, kinins are known to mediate inflammation, a cardinal feature of which is pain, and the clearest evidence for a primary neuronal role exists so far in the activation by kinins of peripherally located nociceptive receptors on C-fibre terminals that transmit and modulate pain perception. Kinins are also important in vascular homeostasis, the release of excitatory amino acid neurotransmitters, and the modulation of cerebral cellular immunity. The two kinin receptors, B2 and B1, that modulate the cellular actions of kinins have been demonstrated in animal neural tissue, neural cells in culture, and various areas of the human brain. Their localisation in glial tissue and neural centres, important in the regulation of cardiovascular homeostasis and nociception, suggests that the kinin system may play a functional role in the nervous system.
哺乳动物的神经系统和外周组织含有大量生物活性肽和蛋白酶，它们在神经系统中作为神经递质或神经调节剂发挥作用，在外周组织中作为激素或细胞介质发挥作用，并在人类神经疾病中起作用。本综述讨论了缓激肽和胰激肽（肽类）、激肽释放酶（蛋白水解酶）和激肽酶（肽酶）在神经生理学和神经病理状态下的存在及其可能的功能相关性。组织激肽释放酶是主要的细胞激肽生成酶，已定位在哺乳动物大脑的各个区域。在功能上，它还可能有助于脑蛋白的正常更新以及肽类激素、神经递质和一些对正常神经元功能和突触传递至关重要的神经生长因子的加工。一类特定的激肽酶，即负责快速降解激肽的肽酶，被认为与脑啡肽酶A相同。此外，已知激肽可介导炎症，其主要特征是疼痛，迄今为止，激肽激活C纤维终末外周伤害性感受器从而传递和调节痛觉，这是激肽在初级神经元中发挥作用的最明确证据。激肽在血管稳态、兴奋性氨基酸神经递质的释放以及脑细胞免疫调节中也很重要。调节激肽细胞作用的两种激肽受体B2和B1已在动物神经组织、培养的神经细胞和人类大脑的各个区域得到证实。它们在胶质组织和神经中枢中的定位，对心血管稳态和伤害感受的调节很重要，这表明激肽系统可能在神经系统中发挥功能作用。
