Central and peripheral antiulcer and antisecretory effects of Ala5NKA(4-10), a tachykinin NK2 receptor agonist, in rats.
Analogs of NKA(4-10) which are selective tachykinin NK2 receptor agonists have been tested as anti-secretory and anti-ulcer agents in 2-h pylorus ligation in rats. Peripheral (500 micrograms/kg s.c.) or central (5 micrograms/rat i.c.v.) administration of Ala5NKA(4-10), but not NKA(4-10) or Ala5[beta Ala8]NKA(4-10), inhibited gastric ulcer and secretion. The same effective doses of Ala5NKA(4-10) did not influence gastric emptying. The anti-secretory and anti-ulcer effects of Ala5NKA(4-10) were antagonized by pretreatment with the tachykinin NK2 receptor antagonist MEN 10,627 at a dose (250 micrograms/kg s.c.) which did not affect gastric secretion and ulcers. These findings provide the first evidence that activation of central and peripheral tachykinin NK2 receptors affords protection against gastric ulcers induced by 2 h pylorus ligation in rats, by reducing gastric acid secretion.
Improta
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Institute of Medical Pharmacology, University La Sapienza, Rome, Italy.
Broccardo
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Tabacco
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Evangelista
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D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D005744:Gastric Acid / Q000378:metabolism*; D008297:Male; D015288:Neurokinin A / Q000031:analogs & derivatives* / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018041:Receptors, Neurokinin-2 / Q000819:agonists*; D012636:Secretory Rate / Q000187:drug effects
D000897:Anti-Ulcer Agents; D010446:Peptide Fragments; D018041:Receptors, Neurokinin-2; C110303:neurokinin A (4-10), Ala(5)-; D015288:Neurokinin A