Identification and functional importance of IL-1 receptors on rat parietal cells

Abstract

We studied the expression of interleukin-1 (IL-1) receptors and the effect of IL-1β on the function of highly enriched (>97%) rat parietal cells. RT-PCR of parietal cell poly(A)+RNA with primers specific for the rat IL-1 receptor revealed a single 547-kb PCR product highly homologous to the published sequence of the IL-1 receptor. Northern blot analysis of poly(A)+RNA of rat parietal cells and brain revealed a single RNA species of 5.7 kb. Cytochemistry of parietal cell IL-1 receptor was performed with biotinylated recombinant human IL-1β, visualized by avidin-coupled fluorescein. Corresponding to the high degree of parietal cell enrichment, 95% of the cells stained positive. Basal H+production ([14C]aminopyrine accumulation) was not changed by IL-1β (0.25–100 pg/ml) nor was the response to histamine or carbachol when added simultaneously with the cytokine. However, when parietal cells were preincubated with IL-1β (0.5–5 pg/ml) for 10 min before the addition of histamine or carbachol, the response to these secretagogues was reduced by 35 and 67%, respectively. Inhibition by IL-1β was fully reversed by the human recombinant IL-1 receptor antagonist. Preincubation of parietal cells with IL-1β failed to alter histamine-stimulated cAMP production but markedly inhibited carbachol-induced formation ofd- myo-inositol 1,4,5-trisphosphate. In fura 2-loaded, purified parietal cells, 10 min preincubation with IL-1β dramatically reduced the initial transient peak elevation of intracellular Ca2+concentration in response to carbachol. We conclude that rat parietal cells express IL-1 receptors mediating inhibition of H+production. The antisecretory effect of IL-1β may contribute to hypoacidity secondary to acute Helicobacter pylori infection or during chronic colonization by H. pylori preferring the fundic mucosa.