HEPARIN INHIBITS HISTAMINE-RELEASE FROM CANINE MAST-CELLS

To determine the role of heparin in mast cell exocytosis, we studied t he effect of heparin on histamine release induced by compound 48/80 or calcium ionophore A23187 in canine mastocytoma cells (BR). Heparin ca used concentration-dependent inhibition of compound 48/80-induced hist amine 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 inhib ition 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 hepa rin produced a similar inhibitory effect on compound 48/80-induced his tamine release (n = 4; P < 0.05). The inhibitory effect of heparin on histamine release was rapid and was eliminated by washing cells. Dextr an 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-in duced exocytosis in mast cells probably by its negative charge density .