Effects of histamine on inositol phosphates and intracellular Ca2+ in human glomerular epithelial cells |
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Authors: | Spath, M. M. Pavensradt, H. Fischer, R. Schlunck, G. Wanner, C. Schollmeyer, P. |
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Affiliation: | Medizinische Universitätsklinik, Abteilung Innere Medizin IV Freiburg, Germany |
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Abstract: | The effect of histamine on the phosphoinositide turnover andintracellular free calcium activity [Ca2+]i was examined inhuman glomerular epithelial cells in culture. Addition of histamineto glomerular epithelial cells resulted in formation of inositolphosphates in a time- and dose-dependent manner. A transientmaximum of inositol trisphosphate (InsP3) was observed within10 s. Stimulation of protein kinase C by short-term pretreatment(15 mm) of glom erular epithelial cells with phorbol 12-mynstate13-acetate caused a dose-dependent inhibition of the histamine-inducedinositol phosphate accumulation. The baseline of [Ca2+]i inthe cells was 115 ±2.7 nmol/l (n=103). Histamine (ED50:approx. 2x107mol/l) caused a rapid and transient increasein [Ca2+]i, as detected by fura-2 microfluorimetry studies.In a calcium-free extracellular solution the rapid increaseof [Ca2+]i was still present. The H1 receptor antagonist mepyramine(IC50: approx. 8 x 109 mol/l) inhibited the histamine(106 mol/l) response on [Ca2+]i Cimetidine, a potentH2 receptor antagonist, showed no effect. This data indicates that H1 receptor activation causes hydrolysisof phosphatidylinositol 4, 5-bisphosphate by phospholipase Cactivation, and consecutive mobil ization of intracellular calcium.Since histamine is a mediator of inflammation, antigen responseand cellular injury, these findings could be of importance forthe understanding of glomerular epithelial cell pathology. |
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Keywords: | cimetidine fura-2 glomerulus H1 receptor mepyramine phospholipase C |
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