title: Effects of loratadine on cytosolic Ca2+ levels and leukotriene release: novel mechanisms of action independent of the anti-histamine activity.
abstract: Loratadine, a non-sedating anti-histamine drug, displays in vitro potential anti-allergic properties not related to its interaction with the histamine H1 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.
authors.affiliation: Institute of Pharmacological Sciences, University of Milan, Italy.
authors.forename: O
authors.initials: O
authors.lastname: Letari
authors.forename: A
authors.initials: A
authors.lastname: Miozzo
authors.forename: G
authors.initials: G
authors.lastname: Folco
authors.forename: P A
authors.initials: PA
authors.lastname: Belloni
authors.forename: A
authors.initials: A
authors.lastname: Sala
authors.forename: G E
authors.initials: GE
authors.lastname: Rovati
authors.forename: S
authors.initials: S
authors.lastname: Nicosia
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000097:blood / Q000378:metabolism*; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007124:Immunoenzyme Techniques; D015289:Leukotrienes / Q000378:metabolism*; D017336:Loratadine / Q000031:analogs & derivatives / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D011969:Receptors, Histamine H1 / Q000187:drug effects*; D016593:Terfenadine / Q000494:pharmacology; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin
chemical_list: D015289:Leukotrienes; D011969:Receptors, Histamine H1; D013729:Terpenes; C086094:des(ethoxycarbonyl)loratadine; D019284:Thapsigargin; D017336:Loratadine; D016593:Terfenadine; D002118:Calcium