Heparin inhibits histamine release from canine mast cells.
To determine the role of heparin in mast cell exocytosis, we studied the effect of heparin on histamine release induced by compound 48/80 or calcium ionophore A23187 in canine mastocytoma cells (BR). Heparin caused concentration-dependent inhibition of compound 48/80-induced histamine release from mast cells (n = 4; P < 0.05) with a mean inhibitory concentration of 0.14 +/- 0.01 U/ml (mean +/- SE). Mean maximal inhibition was 69.3 +/- 2.0%. In contrast, heparin had no effect on calcium ionophore A23187-induced histamine release. Although benzyl alcohol, a preservative of pharmaceutical heparin, had no effect, purified heparin produced a similar inhibitory effect on compound 48/80-induced histamine release (n = 4; P < 0.05). The inhibitory effect of heparin on histamine release was rapid and was eliminated by washing cells. Dextran sulfate, a polysaccharide with negative charge density, produced a similar inhibitory effect on compound 48/80-induced histamine release (n = 4; P < 0.05). We conclude that heparin inhibits compound 48/80-induced exocytosis in mast cells probably by its negative charge density.
Inase
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Cardiovascular Research Institute, University of California, San Francisco 94143.
Schreck
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Lazarus
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D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D016264:Dextran Sulfate / Q000494:pharmacology; D004285:Dogs; D006493:Heparin / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects*; D007700:Kinetics; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D012515:Mast-Cell Sarcoma / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D000001:Calcimycin; D003189:p-Methoxy-N-methylphenethylamine; D006493:Heparin; D016264:Dextran Sulfate