Central and peripheral antiulcer and antisecretory effects of Ala 5NKA(4–10), a tachykinin NK 2 receptor agonist, in rats

Abstract

Analogs of NKA(4–10) which are selective tachykinin NK 2 receptor agonists have been tested as antisecretory and anti-ulcer agents in 2-h pylorus ligation in rats. Peripheral (500 μg/kg s.c.) or central (5 μg/rat i.c.v.) administration of Ala 5NKA(4–10), but not NKA(4–10) or Ala 5[βAla 8]NKA(4–10), inhibited gastric ulcer and secretion. The same effective doses of Ala 5NKA(4–10) did not influence gastric emptying. The anti-secretory and anti-ulcer effects of Ala 5NKA(4–10) were antagonized by pretreatment with the tachykinin NK 2 receptor antagonist MEN 10,627 at a dose (250 μg/kg s.c.) which did not affect gastric secretion and ulcers. These findings provide the first evidence that activation of central and peripheral tachykinin NK 2 receptors affords protection against gastric ulcers induced by 2 h pylorus ligation in rats, by reducing gastric acid secretion.