Central and peripheral effects of prostaglandin E2 and enprostil on gastric acid secretion in the rat.
The intracerebroventricular (i.c.v.) administration of prostaglandin E2 (PGE2) inhibits gastric secretion at doses that are inactive by i.v. administration in the rat. The present study was undertaken to examine the central and peripheral effects of enprostil, a potent synthetic PGE2 analogue, on gastric acid secretion as compared to those of PGE2. We used conscious rats equipped with a chronic gastric fistula and a cannula to allow injection into the third ventricle of the brain. Gastric acid output was measured under basal interdigestive conditions and during stimulation with submaximal doses of pentagastrin and histamine. Total inhibition of basal and stimulated gastric acid output was obtained after i.c.v. PGE2 and after i.c.v. or i.v. enprostil administration. After i.v. PGE2, the maximal observed inhibition was not greater than 50%. The ratio of ED50 values for i.v. administered to i.c.v. administered PGE2 was 64 or more, whereas the ratio of ED50 values for i.v. enprostil to i.c.v. enprostil was 9 to 13. Under all conditions studied, enprostil was more potent than PGE2 and this greater potency was more prominent after i.v. administration (ratio 250 to 2500) than after i.c.v. administration (ratio 10 to 400). The blockade of alpha 2-adrenoceptors by idazoxan did not suppress the inhibition of gastric secretion produced by i.c.v. PGE2 or enprostil. It is concluded that low doses of PGE2 inhibit gastric acid output mainly through a central mechanism, whereas low doses of enprostil potently inhibit gastric acid output through both a central and a peripheral mechanism. alpha 2-Adrenoceptors are not essential for the effect of i.c.v. prostanoids on gastric acid secretion.
INSERM U239, Faculté X. Bichat, Paris, France.
D
D
Sautereau
M
M
Chicau-Chovet
A
A
Tsocas
C
C
Rozé
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects*; D015232:Dinoprostone / Q000008:administration & dosage / Q000494:pharmacology*; D004146:Dioxanes / Q000494:pharmacology; D016620:Enprostil; D005744:Gastric Acid / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D019329:Idazoxan; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D010418:Pentagastrin / Q000494:pharmacology; D010525:Peripheral Nerves / Q000187:drug effects*; D011459:Prostaglandins E, Synthetic / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D011459:Prostaglandins E, Synthetic; D006632:Histamine; D010418:Pentagastrin; D016620:Enprostil; D015232:Dinoprostone; D019329:Idazoxan