Evangelista S, Lippe I T, Rovero P, Maggi C A, Meli A
Department of Pharmacology, A. Menarini Pharmaceuticals, Firenze, Italy.
Peptides. 1989 Jan-Feb;10(1):79-81. doi: 10.1016/0196-9781(89)90080-6.
Subcutaneous pretreatment of rats with neurokinin (NK) A or the fragment NKA(4-10) reduced the degree of gastric lesions induced by oral administration of 96% ethanol. The protective effect of NKA(4-10) was dose-dependent. Arg-NKB, the water soluble derivative of NKB, was less effective than NKA or NKA(4-10) while [Me-Phe7]NKB, substance P (SP) and SP-methyl-ester were inactive. The NKA(4-10) antilesion effect was reversed by pretreatment with N-ethyl-maleimide, suggesting a possible involvement of sulphydryls in its action. Among the nonmammalian tachykinins, kassinin significantly reduced ethanol-induced lesions while eledoisin and physalaemin at equivalent molar doses were inactive. These results provide, for the first time, evidence that tachykinins and their derivatives exert gastroprotective activity toward ethanol-induced haemorrhagic lesions. Assuming a receptor-mediated mechanism, NK-2 sites could be involved.
用神经激肽（NK）A或片段NKA(4 - 10)对大鼠进行皮下预处理，可减轻口服96%乙醇所致的胃损伤程度。NKA(4 - 10)的保护作用呈剂量依赖性。NKB的水溶性衍生物精氨酸 - NKB的效果不如NKA或NKA(4 - 10)，而[甲基 - 苯丙氨酸7]NKB、P物质（SP）和SP - 甲酯则无活性。用N - 乙基 - 马来酰亚胺预处理可逆转NKA(4 - 10)的抗损伤作用，提示巯基可能参与其作用。在非哺乳动物速激肽中，蛙皮素能显著减轻乙醇诱导的损伤，而等摩尔剂量的eledoisin和雨蛙素则无活性。这些结果首次提供了证据，表明速激肽及其衍生物对乙醇诱导的出血性损伤具有胃保护活性。假设存在受体介导机制，NK - 2位点可能参与其中。
