Effects of histamine on inositol phosphates and intracellular Ca2+ in human glomerular epithelial cells.
The effect of histamine on the phosphoinositide turnover and intracellular free calcium activity [Ca2+]i was examined in human glomerular epithelial cells in culture. Addition of histamine to glomerular epithelial cells resulted in formation of inositol phosphates in a time- and dose-dependent manner. A transient maximum of inositol trisphosphate (InsP3) was observed within 10 s. Stimulation of protein kinase C by short-term pretreatment (15 min) of glomerular epithelial cells with phorbol 12-myristate 13-acetate caused a dose-dependent inhibition of the histamine-induced inositol phosphate accumulation. The baseline of [Ca2+]i in the cells was 115 +/- 2.7 nmol/l (n = 103). Histamine (ED50: approx. 2 x 10(-7) mol/l) caused a rapid and transient increase in [Ca2+]i as detected by fura-2 microfluorimetry studies. In a calcium-free extracellular solution the rapid increase of [Ca2+]i was still present. The H1 receptor antagonist mepyramine (IC50: approx. 8 x 10(-9) mol/l) inhibited the histamine (10(-6) mol/l) response on [Ca2+]i. Cimetidine, a potent H2 receptor antagonist, showed no effect. This data indicates that H1 receptor activation causes hydrolysis of phosphatidylinositol 4, 5-bisphosphate by phospholipase C activation, and consecutive mobilization of intracellular calcium. Since histamine is a mediator of inflammation, antigen response and cellular injury, these findings could be of importance for the understanding of glomerular epithelial cell pathology.
Medizinische Universitätsklinik, Abteilung Innere Medizin IV, Freiburg, Germany.
M M
MM
Späth
H
H
Pavenstädt
R
R
Fischer
G
G
Schlunck
C
C
Wanner
P
P
Schollmeyer
D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002927:Cimetidine / Q000494:pharmacology; D003592:Cytophotometry; D004789:Enzyme Activation; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D011738:Pyrilamine / Q000494:pharmacology; D015290:Second Messenger Systems / Q000187:drug effects
D007295:Inositol Phosphates; D002927:Cimetidine; D006632:Histamine; D011493:Protein Kinase C; D011738:Pyrilamine; D002118:Calcium