On the mechanism of histamine release induced by thapsigargin from Thapsia garganica L

Thapsigargin (Tg) is a pure chemical compound isolated from Thapsia garganica with a molecular weight of 650. It releases histamine from isolated rat mast cells but not from isolated histamine-retaining mast cell granules. The rate of release is markedly influenced by pretreatment of mast cells with Tg prior to the addition of calcium. In agreement with the effect of the ionophore A23187 but in contrast to many other calcium-dependent histamine-releasing agents, cells preincubated with Tg respond to the secretory action of calcium whenever the ion is introduced. However, after dilution of Tg-pretreated cells histamine release induced by the addition of calcium became dependent on the time of its addition. The secretory reaction induced by Tg and calcium can be divided into a two-step reaction at 37 degrees C. Pretreatment of mass cells with Tg renders the cells insensitive to the secretory action of compound 48/80 in the absence of calcium, and this effect could be partly counteracted if 1 mM of strontium was added together with compound 48/80. It is concluded that among various calcium- and energy-dependent histamine-releasing agents Tg most closely resembles the action of fluoride on isolated rat mast cells.