Nadobna G

Treatment with Ebastine Changes Expression of Histamine H1 and H2 Receptor mRNA on Peripheral Blood Mononuclear Cells

AbstractBackground: Histamine H1 and H2 receptors both belong to a family of G protein-coupled receptors that often show opposite actions on cell activity. Ebastine, a piperidine derivative, and its active metabolite, carebastine, are very potent second-generation histamine H1 receptor antagonists. Objective: To investigate the influence of treatment with ebastine on the expression of histamine H1 receptor and H2 receptor mRNA on peripheral blood mononuclear cells (PBMC). Patients: The study was performed in five grass pollen-allergic individuals with seasonal allergic rhinitis. All subjects showed positive skin-prick tests with mixed grass pollen. The study was performed out of the grass pollen season. Methods: Blood samples were obtained before and after treatment with ebastine (Kestine®, Rhône-Poulenc-Rorer, France) 10 mg/day for 7 days. PBMC were isolated using density-gradient centrifugation. Histamine H1 and H2 receptor mRNA expression were determined using semiquantitative reverse transcription polymerase chain reaction. Results: Prior to ebastine treatment, mRNA expression measured by the peak area for histamine H1 and H2 receptors was 33, 323 (± 33, 269) relative fluorescence units (RFU)and 59, 511 (± 31, 621) RFU, respectively. After treatment, histamine H1 and H2 receptor mRNA expression increased to 42, 061 (± 28, 263 ) and 89, 913 (+ 13, 053) RFU, respectively, and this difference was statistically significant (p < 0.01) in contrast to the difference prior to the treatment. Ebastine-induced histamine H1 and H2 receptor upregulation, however, moved the balance towards histamine H2 receptor dominance. Conclusions: In conclusion, ebastine induced H1 and H2 receptor upregulation, but moved the balance towards H2 receptor dominance. This potent H1 receptor antagonist, in addition to reducing allergic symptoms, is able to influence inflammatory responses. Since H2 receptor stimulation shows suppressive effects on cell activation, this can contribute to long-term anti-inflammatory actions of anti-histamines.