Activation and inhibition of calcium‐dependent histamine secretion by ATP ions applied to rat mast cells.

Abstract

The concentration dependence on ATP of [rat] mast cell histamine secretion in the presence of various concentrations of Mg2+ and Ca2+ confirms that the agonist form of ATP is the free form of ATP (ATP(free)) not bound to divalent cations, i.e., ATP4-.It induces 50% activation at about 1.2 .mu.M, maximal secretion at about 2.7 .mu.M and 50% self-inhibition at about 4.4 .mu.M. The divalent cations Mg2+ and Ca2+ were used to buffer ATP(free) in the range 1-8 .mu.M in the presence of much higher concentrations of ATP(total). In addition to its effect as a buffer for ATP, Ca2+ is required for secretion. With ATP(free) at 1 .mu.M, the time-course of histamine secretion is characterized by a delay of about 10 min before secretion commences. With increasing concentration of ATP(free) the delay becomes shorter (< 5 min with ATP(free) at 2 .mu.M). Secretion commences promptly on addition of Ca2+ to cells pretreated with low concentrations of ATP(free) (< 2 .mu.M). Apparently the delay normally observed represents the time taken for Ca2+ sensitivity to develop (i.e., probably the time taken for Ca2+ channels to open). Late addition of Ca2+ to cells pretreated with higher concentrations of ATP(free) (> 2 .mu.M) results in a reduced amount of histamine secretion compared to that which normally occurs. This reduction (which increases with time of exposure to ATP) and the self-inhibition due to higher concentrations of ATP(free) may be 2 facets of a common inhibitory mechanism. These results are discussed in relation to the observation that mast cells treated with ATP(free) at self-inhibitory concentrations become permeable to phosphorylated metabolites and nucleotides.