Roles of endogenous leukotrienes in damage caused by ethanol in isolated rat gastric cells.
The activity of prostaglandin (PG) and leukotriene (LT) synthesis and the role of endogenous LT in cellular resistance were assessed in isolated parietal and nonparietal cells of rats. Rat gastric cells were isolated and the fractions rich (F1) and poor (F2) in parietal cells were obtained. In F1, more PGE2, PGI2 (measured as the stable metabolite 6-keto-PGF1 alpha), and sulfidopeptide (SP)-LTs and less thromboxane A2 (TXA2, measured as the stable metabolite TXB2) were synthesized than in F2. AA861, an inhibitor of 5-lipoxygenase, inhibited the synthesis of SP-LTs in both fractions in a dose-related way. AA861 alone at any concentrations used did not affect the viability of the cells, but prevented the cell damage caused by ethanol in both fractions, the effect of AA861 being inhibited by indomethacin. These results suggest that in rat stomach, PGs and LTs, except TX, are synthesized mainly in parietal cells rather than in nonparietal cells. Endogenous LT may play a crucial role in the development of cellular damage caused by ethanol independently of systemic and extracellular factors. The balance of PG and LT may be important for regulation of cellular resistance.
D000818:Animals; D016227:Benzoquinones; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis; D011464:Epoprostenol / Q000096:biosynthesis; D000431:Ethanol / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D015289:Leukotrienes / Q000502:physiology*; D008297:Male; D010295:Parietal Cells, Gastric / Q000187:drug effects / Q000502:physiology; D011809:Quinones / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013928:Thromboxane A2 / Q000096:biosynthesis
D016227:Benzoquinones; D015289:Leukotrienes; D011809:Quinones; D000431:Ethanol; D013928:Thromboxane A2; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; D011464:Epoprostenol; D015232:Dinoprostone