The effect of recombinant cytokines on [14C]-aminopyrine accumulation by isolated canine parietal cells.
Interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) have been shown to inhibit basal and pentagastrin-stimulated gastric secretion in rats and histamine-stimulated secretion in dogs. IL-1 also reduces the severity of ethanol and stress-induced gastroduodenal damage. The aim of this study was to examine the effects of human recombinant IL-1 alpha and TNF-alpha on enzymatically dispersed and enriched (> 90%) parietal cells stimulated with histamine, histamine plus 3-isobutyl-1-methylxanthine (IMX) or carbachol (all 10(-5) M). Acid secretion was assessed indirectly by quantitating [14C]-aminopyrine (AP) accumulation. IL-1 alpha (500 and 1000 ng/ml) inhibited histamine-stimulated AP uptake by 53% and 60% respectively, and it inhibited IL-1 alpha (1500 ng/ml) by 69%. IL-1 alpha (500 and 1000 ng/ml) inhibited histamine plus IMX-stimulated AP uptake by 36% and 34%, respectively. IL-1 alpha (500 ng/ml) also inhibited carbachol-stimulated AP accumulation. TNF-alpha (100 and 250 ng/ml) inhibited histamine-stimulated AP accumulation by 38% and 36%, respectively. TNF-alpha also significantly inhibited histamine/IMX- and carbachol-stimulated AP uptake (P < or = .01). Indomethacin did not affect IL-1 alpha-induced inhibition. These results show that IL-1 alpha and TNF-alpha inhibit histamine- and carbachol-stimulated isolated parietal cell secretion and that, for IL-1 alpha, this effect does not depend on mucosal prostaglandin synthesis.
Nompleggi
D J
DJ
Harvard Digestive Diseases Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Beinborn
M
M
Roy
A
A
Wolfe
M M
MM
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000632:Aminopyrine / Q000378:metabolism*; D000818:Animals; D002217:Carbachol / Q000037:antagonists & inhibitors; D002250:Carbon Radioisotopes; D002478:Cells, Cultured; D004285:Dogs; D006633:Histamine Antagonists / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1; D010295:Parietal Cells, Gastric / Q000187:drug effects* / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D002250:Carbon Radioisotopes; D006633:Histamine Antagonists; D007375:Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D000632:Aminopyrine; D002217:Carbachol; D015056:1-Methyl-3-isobutylxanthine; D007213:Indomethacin