The Role of Plasma Membrane Ca++‐Mg++ Activated Adenosine Triphosphatase of Rat Mast Cells on Histamine Release

Abstract

The role of a Ca2+-Mg2+ activated ATPase present on the outer surface of rat peritoneal mast cells on histamine release induced by antigen (anaphylactic reaction), compound 48/80 and ionophore A23187 (calcimycin) was studied. A high level of the enzyme activity is retained at the optimal pH for histamine release induced by the 3 releasing agents. The effect of 14 inhibitors of ATPase (quinidine, Fl-, platinum salt, suramin, ethacrynic acid, ethyl alcohol, N-ethylmaleimide, Mn2+, Ni2+, ADP, AMP and the flavones: kaempferol, quercetin and morin) was studied. All the inhibitors, which caused varying degrees of inhibition of ATPase, also inhibited histamine release. The inhibition of the enzyme was competitive with ADP, AMP, ethacrynic acid, suramin and morin and non-competitive with the others. The degree of inhibition of ATPase and of histamine release tended to be similar with 6 inhibitors. With the others the extent of the inhibition of the release and of the enzyme varied. But a marked inhibition of the enzyme was always associated with a pronounced inhibition of histamine release. ATP in lower concentrations (10-20 .mu.M) potentiated histamine release induced by all the 3 releasers, possibly through its utilization by plasma membrane ATPase. The hypothesis that plasma membrane ATPase participates in the histamine release process is supported.