SOME CHARACTERISTICS OF THE ATP-INDUCED HISTAMINE-RELEASE FROM AND PERMEABILIZATION OF RAT MAST-CELLS

Extracellular adenosine 5'-triphosphate (ATP) induced a characteristic , dose-dependent release of histamine and prostaglandin D2 (PGD2) from rat peritoneal mast cells. The process was relatively slow, non-cytot oxic, maximal at physiological pH and dependent on external calcium. S trontium and barium ions were able to substitute for calcium, although higher concentrations were required for maximal release. Cells stimul ated in the absence of calcium progressively lost the ability to respo nd to subsequent reintroduction of the cation. The secretion of histam ine induced by ATP was largely unaffected by the anti-asthmatic drugs disodium cromoglycate and nedocromil sodium but was inhibited by struc turally related flavonoids and by cAMP-active drugs. Importantly, the non-hydrolysable guanosine 5'-triphosphate (GTP) analogue, GTP-gamma-S , elicited a dose-dependent release of histamine when introduced into mast cells permeabilized with ATP in the absence of external calcium. ATP thus appears to be a useful cell permeabilizing tool with which to study the biochemical processes involved in mast cell activation.