Identification and functional importance of IL-1 receptors on rat parietal cells.
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.
Schepp
W
W
Department of Medicine II, Bogenhausen Academic Teaching Hospital, D-81925 Munich, Germany.
Dehne
K
K
Herrmuth
H
H
Pfeffer
K
K
Prinz
C
C
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000276:immunology; D002217:Carbachol / Q000494:pharmacology; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D017931:DNA Primers; D005260:Female; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology*; D010295:Parietal Cells, Gastric / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000494:pharmacology
D017931:DNA Primers; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D006632:Histamine; D002217:Carbachol; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine