Abstract
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 haemorragic lesions. Assuming a receptor-mediated mechanism, NK-2 sites could be involved.
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