Loratadine, a non-sedating anti-histamine drug, displays in vitro potential anti-allergic properties not related to its interaction with the histamine H-1 receptor. In a search for the mechanisms of these actions, we have found that loratadine induces an elevation of cytosolic calcium 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. This in turn brings about the inhibition of [Ca2+](i) rise induced by physiological activators (platelet activating factor and ADP), as well as by thapsigargin. One of the active metabolites of loratadine, descarbo-ethoxy-loratadine, and another anti-histamine, namely terfenadine, exhibit the same effects. In addition, loratadine partially inhibits antigen-induced leukotriene release from human bronchi, but is unable to inhibit the concomitant contraction. We conclude that loratadine can interfere with the mechanisms controlling Ca2+ release, thus inhibiting the cell activation elicited by various agonists through [Ca2+](i) elevation. This might be the mechanism underlying its anti-allergic actions in vitro. Furthermore, loratadine might represent an interesting tool in the study of Ca2+ homeostasis.
EFFECTS OF LORATADINE ON CYTOSOLIC CA2+ LEVELS AND LEUKOTRIENE RELEASE - NOVEL MECHANISMS OF ACTION INDEPENDENT OF THE ANTIHISTAMINE ACTIVITY / O. LETARI, A. MIOZZO, G. FOLCO, P. BELLONI, A. SALA, G. ROVATI, S. NICOSIA. - In: EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION. - ISSN 0922-4106. - 266:3(1994), pp. 219-227.
|Titolo:||EFFECTS OF LORATADINE ON CYTOSOLIC CA2+ LEVELS AND LEUKOTRIENE RELEASE - NOVEL MECHANISMS OF ACTION INDEPENDENT OF THE ANTIHISTAMINE ACTIVITY|
ROVATI, GIANENRICO (Penultimo)
NICOSIA, SIMONETTA (Ultimo)
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||1994|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/0922-4106(94)90130-9|
|Appare nelle tipologie:||01 - Articolo su periodico|