The role of plasma membrane Ca++-Mg++ activated adenosine triphosphatase of rat mast cells on histamine release.

Abstract

The role of a Ca++-MG++ activated ATPase, demonstrated on the outer surface of rat peritoneal mast cells, on histamine release induced by antigen (anaphylactic reaction), compound 48/80 and ionophore A23187 has been studied. A high level of the enzyme activity is retained at the optimal pH for histamine release induced by the three releasing agents. The effect of fourteen inhibitors of ATPase has been studied, viz. quinidine, fluoride, platinum salt, suramin, ethacrynic acid, ethyl alcohol, N-ethylmaleimide, Mn++, Ni++, ADP, AMP and the flavones: kaempferol, quercetin, morin. 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 six 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 microM) has been shown to potentiate histamine release induced by all the three releasers, possibly through its utilization by plasma membrane ATPase. The observations agree with the hypothesis that plasma membrane ATPase participates in the histamine release process.