EFFECTS OF LORATADINE ON CYTOSOLIC CA2- NOVEL MECHANISMS OF ACTION INDEPENDENT OF THE ANTIHISTAMINE ACTIVITY( LEVELS AND LEUKOTRIENE RELEASE )

Loratadine, a non-sedating anti-histamine drug, displays in vitro pote ntial anti-allergic properties not related to its interaction with the histamine H-1 receptor. In a search for the mechanisms of these actio ns, we have found that loratadine induces an elevation of cytosolic ca lcium ion, [Ca2+](i), in rat peritoneal macrophages or human platelets . The mechanism of this elevation resides in the ability of loratadine to discharge intracellular Ca2+ stores, similarly to thapsigargin. Th is in turn brings about the inhibition of [Ca2+](i) rise induced by ph ysiological activators (platelet activating factor and ADP), as well a s by thapsigargin. One of the active metabolites of loratadine, descar bo-ethoxy-loratadine, and another anti-histamine, namely terfenadine, exhibit the same effects. In addition, loratadine partially inhibits a ntigen-induced leukotriene release from human bronchi, but is unable t o inhibit the concomitant contraction. We conclude that loratadine can interfere with the mechanisms controlling Ca2+ release, thus inhibiti ng the cell activation elicited by various agonists through [Ca2+](i) elevation. This might be the mechanism underlying its anti-allergic ac tions in vitro. Furthermore, loratadine might represent an interesting tool in the study of Ca2+ homeostasis.