Tachykinins protect against ethanol-induced gastric lesions in rats.
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.
Evangelista
S
S
Department of Pharmacology, A. Menarini Pharmaceuticals, Firenze, Italy.
Lippe
I T
IT
Rovero
P
P
Maggi
C A
CA
Meli
A
A
D000818:Animals; D000431:Ethanol / Q000037:antagonists & inhibitors / Q000633:toxicity*; D005033:Ethylmaleimide / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013270:Stomach / Q000187:drug effects / Q000473:pathology*; D015320:Tachykinins / Q000494:pharmacology*
D015320:Tachykinins; D000431:Ethanol; D005033:Ethylmaleimide; D007213:Indomethacin