Role of central prostaglandin E2 in the regulation of gastric acid secretion in the rat.
The central action of prostaglandin E2 (PGE2) on gastric acid secretion was investigated in rats by comparing the effects of intracisternal (i.ci.) and i.v. administration of PGE2 and the influence of i.ci. injection of indomethacin on acid secretion and PGE2 generation in the brain and stomach. I.ci. injections of PGE2 (1-10 micrograms) or the stable analog, 16,16-dimethyl PGE2, (0.01-0.1 micrograms) induced a dose dependent inhibition of baclofen-stimulated gastric acid secretion by 0-82% and by 7-87% respectively. I.v. infusion of PGE2 also induced a dose related inhibition of baclofen-stimulated acid secretion, but 10 fold higher doses were required. I.ci. or i.v. injection of indomethacin in doses ranging from 50 to 500 micrograms/rat, produced a similar dose dependent inhibition of the PGE2 generation in both the gastric mucosa and brain cortex measured 1 h post injection. I.ci. injection of indomethacin (500 micrograms) increased within 10 min acid secretion with a peak response at 20-30 min; 60-120 min post injection, when prostaglandin synthesis was inhibited by 90%, basal and baclofen-stimulated acid output were not altered. These results further establish that PGE2 acts in the brain to inhibit vagally stimulated gastric acid secretion in rats, and do not support a tonic inhibitory influence of endogenous brain PGE2 in the regulation of gastric acid secretion. In addition, these data showed that indomethacin injected i.ci. at 500 micrograms does not induce a selective inhibition of prostaglandin synthesis in the brain.
Saperas
E
E
Center for Ulcer Research and Education, VA Wadsworth Medical Center, Los Angeles, CA.
Kauffman
G
G
Taché
Y
Y
D015064:16,16-Dimethylprostaglandin E2 / Q000134:cerebrospinal fluid / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D002946:Cisterna Magna; D015232:Dinoprostone / Q000134:cerebrospinal fluid / Q000494:pharmacology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D007262:Infusions, Intravenous; D007267:Injections; D008297:Male; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology
D011453:Prostaglandins; D001418:Baclofen; D015232:Dinoprostone; D015064:16,16-Dimethylprostaglandin E2; D007213:Indomethacin