Inhibition by 16,16-dimethyl PGE2 of ethanol-induced gastric mucosal damage and leukotriene B4 and C4 formation.
The effects of PGE2 and its stable analogue, 16,16 dimethyl PGE2 (dmPGE2) were investigated on ethanol-induced gastric mucosal haemorrhagic lesions and leukotriene formation in the rat. Exposure of the rat gastric mucosa to ethanol in-vivo, produced a concentration-related increase in the mucosal formation of leukotriene B4 (LTB4) which was correlated with macroscopically-apparent haemorrhagic damage to the mucosa. Challenge with absolute ethanol likewise enhanced the mucosal formation of LTC4 whereas the mucosal formation of 6-keto-PGF1 alpha was unaffected. Challenge of the rat gastric mucosa in vitro with ethanol induced a concentration-dependent increase in the formation of LTB4 and LTC4, but not 6-keto PGF1 alpha. Pretreatment with PGE2 (200-500 micrograms/kg p.o.) prevented the haemorrhagic mucosal damage induced by oral administration of absolute ethanol but not the increased formation of leukotrienes by the mucosa. In contrast, pretreatment with a high dose of dmPGE2 (20 micrograms/kg p.o.) prevented both the gastric mucosal lesions and the increase mucosal leukotriene formation. The differences in the effects of these prostaglandins may be related to the nature or degree of protection of the gastric mucosa. Thus, high doses of dmPGE2 but not PGE2 may protect the cells close to the luminal surface of the mucosa and hence reduce the stimulation of leukotriene synthesis by these cells.
Boughton-Smith
N K
NK
Department of Pharmacology, Wellcome Research Laboratories Beckenham, Kent, U.K.
Whittle
B J
BJ
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D000431:Ethanol / Q000633:toxicity*; D005753:Gastric Mucosa / Q000187:drug effects*; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000096:biosynthesis*; D008297:Male; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000096:biosynthesis*
D011459:Prostaglandins E, Synthetic; D013189:SRS-A; D007975:Leukotriene B4; D000431:Ethanol; D015064:16,16-Dimethylprostaglandin E2