Protective and antisecretory effects of the new PGE2 analogue, FCE 20700, and of 16,16 dimethyl PGE2 in pylorus-ligated rat.
Different doses of the new chemically stable PGE2 analogue, FCE 20700, (150, 300, 450, 900, 1200 and 1800 micrograms kg-1) and of 16,16-dimethyl PGE2, DMPGE2, (1, 3, 10, 30 and 100 micrograms kg-1) were administered by gavage to pylorus-ligated rats. The dose-response relationship in preventing gastric mucosal damage and in inhibiting gastric acid and pepsin secretion was investigated. In the same animals, a simultaneous evaluation of barrier and luminal mucus was also performed. Both compounds were markedly active in preventing the macroscopic damage of the gastric mucosa and, at higher doses, in inhibiting gastric acid secretion. FCE 20700 was approximately 100-150 times less potent than DMPGE2. Mucosal protection appeared to be exerted by the two prostaglandins independently of any action on mucus. Furthermore, as the antisecretory doses were approached, a decline in protective activity became evident, suggesting that the dosage of prostaglandins is critical, making it possible to orient their activity either towards mucosal protection or towards acid inhibition.
Morini
G
G
Institute of Pharmacology and Pharmacology, University of Parma, Italy.
Chiavarini
M
M
Barocelli
E
E
Impicciatore
M
M
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology*; D000818:Animals; D015232:Dinoprostone / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology*; D009093:Mucus / Q000032:analysis; D010434:Pepsin A / Q000378:metabolism; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology*; D011708:Pylorus / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013276:Stomach Ulcer / Q000517:prevention & control
D011459:Prostaglandins E, Synthetic; C040808:FCE 20700; D010434:Pepsin A; D015232:Dinoprostone; D015064:16,16-Dimethylprostaglandin E2