Central and peripheral antiulcer and antisecretory effects of Ala(5)NKA(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 antisecretory and anti-ulcer agents in 2-h pylorus ligation in rats. Peripheral (500 mu g/kg s.c.) or central (5 mu g/rat i.c.v.) administration of Ala(5)NKA(4-10), but not NKA(4-10) or Ala(5)[beta Ala(8)]NKA(4-10), inhibited gastric ulcer and secretion. The same effective doses of Ala(5)NKA(4-10) did not influence gastric emptying. The anti-secretory and anti-ulcer effects of Ala(5)NKA(4-10) were antagonized by pretreatment with the tachykinin NK2 receptor antagonist MEN 10,627 at a dose (250 mu g/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.