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Am J Physiol Gastrointest Liver Physiol 275: G1094-G1105, 1998;
0193-1857/98 $5.00
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Vol. 275, Issue 5, G1094-G1105, November 1998

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

Wolfgang Schepp1, Kerstin Dehne2, Hedda Herrmuth2, Klaus Pfeffer3, and Christian Prinz2

1 Department of Medicine II, Bogenhausen Academic Teaching Hospital, D-81925 Munich; and Departments of 2 Medicine II and 3 Medical Microbiology, Immunology, and Hygiene, Technical University of Munich, D-81675 Munich, Germany

We studied the expression of interleukin-1 (IL-1) receptors and the effect of IL-1beta 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-1beta , 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-1beta (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-1beta (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-1beta was fully reversed by the human recombinant IL-1 receptor antagonist. Preincubation of parietal cells with IL-1beta failed to alter histamine-stimulated cAMP production but markedly inhibited carbachol-induced formation of D-myo-inositol 1,4,5-trisphosphate. In fura 2-loaded, purified parietal cells, 10 min preincubation with IL-1beta 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-1beta may contribute to hypoacidity secondary to acute Helicobacter pylori infection or during chronic colonization by H. pylori preferring the fundic mucosa.

interleukin-1; interleukin-1 receptor antagonist; hydrogen production; adenosine 3',5'-cyclic monophosphate; D-myo-inositol 1,4,5-trisphosphate; cytosolic calcium; fluorescence microscopy; fura 2-acetoxymethyl ester


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