The effect of adenosine and its analogues on cyclic AMP changes and histamine secretion from rat peritoneal mast cells stimulated by various ligands.

In keeping with previous reports, immunological activation of purified rat peritoneal mast cells induced a transient elevation in the intracellular concentration of cyclic AMP which preceded or accompanied the release of histamine. Enhancement or suppression of this rise by appropriate adenosine analogues produced parallel changes in histamine secretion. However, the purinoceptor antagonist theophylline prevented the augmented rise in cyclic AMP induced by adenosine analogues but did not affect the enhancement of histamine release. In addition, pharmacological activation of the cell with a number of diverse ligands induced histamine release without any accompanying changes in cyclic AMP. This release was modulated by adenosine analogues in identical fashion to IgE-directed ligands but again without affecting cyclic AMP levels. These data clearly show that adenosine can augment histamine release independently of adenylate cyclase and seriously question the significance of the early rise in cyclic AMP as a causal event in immunological secretion of the amine.