Patacchini R, Maggi C A
Pharmacology Department, A. Menarini Pharmaceuticals, Florence, Italy.
Arch Int Pharmacodyn Ther. 1995 Jan-Feb;329(1):161-84.
The tachykinins, substance P, neurokinin A and neurokinin B, are a family of neuropeptides widely distributed in the mammalian central and peripheral nervous system. In the peripheral nervous system, tachykinins released from peripheral endings of sensory nerves are responsible for the neurogenic inflammation phenomenon. In the spinal cord/central nervous system, tachykinins play a role in pain transmission/perception and in some autonomic reflexes and behaviors. Their actions are mediated by three distinct receptors, termed NK1, NK2 and NK3. All tachykinin receptors belong to the superfamily of G protein-coupled receptors, with seven putative transmembrane spanning segments. In the past few years, a number of potent and selective antagonists, of both peptide and nonpeptide nature, has been developed for the NK1, NK2 and NK3 receptors. The contemporary isolation and cloning of the three tachykinin receptors enable now to study the molecular determinants for the interaction of natural tachykinins with their receptors, and the mechanism by which the antagonists interfere in this process. Furthermore, the introduction of tachykinin antagonists has revealed a striking species-related heterogeneity among the tachykinin receptors, and has also suggested a possible intra-species heterogeneity for both NK1 and NK2 receptors. However, molecular biology studies are needed to prove the existence of true tachykinin receptor subtypes.
速激肽、P物质、神经激肽A和神经激肽B是一族神经肽，广泛分布于哺乳动物的中枢和外周神经系统。在外周神经系统中，感觉神经外周末梢释放的速激肽可引发神经源性炎症现象。在脊髓/中枢神经系统中，速激肽在疼痛传递/感知以及某些自主反射和行为中发挥作用。它们的作用由三种不同的受体介导，分别称为NK1、NK2和NK3。所有速激肽受体都属于G蛋白偶联受体超家族，具有七个假定的跨膜区段。在过去几年中，已经开发出了许多肽类和非肽类的强效选择性拮抗剂，用于作用于NK1、NK2和NK3受体。三种速激肽受体的当代分离和克隆使得现在能够研究天然速激肽与其受体相互作用的分子决定因素，以及拮抗剂干扰这一过程的机制。此外，速激肽拮抗剂的引入揭示了速激肽受体之间存在显著的物种相关异质性，同时也表明NK1和NK2受体在种内可能存在异质性。然而，需要进行分子生物学研究来证实真正的速激肽受体亚型的存在。
