Comparison of prostacyclin and prostaglandin E2 on gastric secretion, gastrin release, and mucosal blood flow in dogs

Abstract

In dogs with gastric fistulae (GF) and Heidenhain pouches (HP), intravenous graded doses of prostacyclin (PGI₂) (dose range: 2.5–20 μg/kg/hr), and prostaglandin E₂ (PGE₂) (dose range: 10–80 μg/kg/hr) produced a dose-dependent inhibition of acid and pepsin secretion stimulated by pentagastrin (3 μg/kg/hr). The ID₅₀ (dose inhibiting acid output by 50%) were 6 μg/kg/hr for PGI₂ and 26 μg/kg/hr for PGE₂ for the GF, and 7 μg/kg/hr for PGI₂ and 22 μg/kg/hr for PGE₂ for the HP. Acid secretion from the GF stimulated by histamine (20 μg/kg/hr) was also inhibited by both prostaglandins: the ID₅₀ were 16 μg/kg/hr for PGI₂ and 22 μg/kg/hr for PGE₂ For the HP, the ID₅₀ were about 20 and 40 μg/kg/hr for PGI₂ and PGE₂, respectively. Meal-induced acid secretion from the GF reached a level similar to that observed in tests with pentagastrin and was inhibited by both prostaglandins. The ID₅₀ were 5 and 20 μg/kg/hr for PGI₂ and PGE₂, respectively. PGI₂ significantly increased serum gastrin above that obtained with meal alone whereas PGE₂ did not affect postprandial serum gastrin. The inhibition of pentagastrin and meal-induced acid secretion was accompanied by a marked reduction in gastric mucosal blood flow (MBF) measured by the [¹⁴C]aminopyrine method, without significant change in the ratio of gastric blood flow to gastric secretion. The MBF in the resting HP mucosa was significantly increased by PGI₂ but reduced by PGE₂. This study shows that PGI₂ is about 3–4 times more potent than PGE₂ in inhibiting pentagastrin and meal-induced gastric secretion and MBF; PGI₂, unlike PGE₂, increases the postprandial serum gastrin and raises the MBF of the resting mucosa. Therefore, both PGI₂ and PGE₂ are antisecretory, but their effects on gastrin release and resting MBF are qualitatively different.