Effects of histamine on inositol phosphates and intracellular Ca2+ in human glomerular epithelial cells

Nephrol Dial Transplant. 1994;9(7):758-63.

Abstract

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.

MeSH terms

  • Calcium / metabolism*
  • Cells, Cultured
  • Cimetidine / pharmacology
  • Cytophotometry
  • Enzyme Activation
  • Epithelial Cells
  • Epithelium / metabolism
  • Histamine / pharmacology*
  • Humans
  • Inositol Phosphates / metabolism*
  • Kidney Glomerulus / cytology
  • Kidney Glomerulus / drug effects
  • Kidney Glomerulus / metabolism*
  • Protein Kinase C / metabolism
  • Pyrilamine / pharmacology
  • Second Messenger Systems / drug effects

Substances

  • Inositol Phosphates
  • Cimetidine
  • Histamine
  • Protein Kinase C
  • Pyrilamine
  • Calcium