Department of Biology and Biotechnology, University of Warmia and Mazury, Oczapowskiego 1A Street, 10-719 Olsztyn, Poland.
J Pharm Pharm Sci. 2019;22(1):93-97. doi: 10.18433/jpps29971.
Fexofenadine (FXF) is the active metabolite of terfenadine with selective peripheral H1 receptor antagonist activity. FXF is a third-generation antihistamine, non-sedating, rapid and very long acting used in symptoms associated with allergic diseases such as allergic rhinitis, asthma and dermatitis. The pleiotropic effects of histamine are mediated by four types of receptors that belong to the G-protein-coupled receptor family: histamine H1 receptor (HRH-1), histamine H2 receptor, histamine H3 receptor, and histamine H4 receptor. Our hypothesis is that HRH-4 opens new possibility in treatment in allergy diseases and FXF could be the antagonist of both HRH-1 and HRH-4.
We isolated a peripheral blood mononuclear cell (PBMC) from children with diagnosed allergies and healthy - control group and measured the HRH-1 and HRH-4 mRNA gene expression using Quantitive Real-Time PCR. We obtained the results from basal gene expression and after FXF and histamine stimulation.
HRH-1 mRNA basal gene expression shows significantly higher, and HRH-4 shows significantly lower expression in allergy group compared to control. In both groups HRH-1 mRNA gene expression was observed as statistically significant increased after histamine stimulation compared to cells not treated, while in HRH-4 only in allergy group we observed statistical increase. FXF successively blocked histamine affinity in HRH-1 mRNA gene expression but not in HRH-4, where we not observed any reaction.
Results clearly overturned our hypothesis about the possibility of using FXF to block over-expression HRH-4 and open new way of treatment in allergy diseases.
非索非那定(FXF)是特非那定的活性代谢物,具有选择性外周 H1 受体拮抗剂活性。FXF 是第三代抗组胺药,无镇静作用,起效快,作用持久,用于治疗与过敏疾病相关的症状,如过敏性鼻炎、哮喘和皮炎。组胺的多效性作用由属于 G 蛋白偶联受体家族的四种类型的受体介导:组胺 H1 受体(HRH-1)、组胺 H2 受体、组胺 H3 受体和组胺 H4 受体。我们的假设是 HRH-4 为过敏疾病的治疗开辟了新的可能性,而 FXF 可能是 HRH-1 和 HRH-4 的拮抗剂。
我们从诊断为过敏的儿童和健康对照组中分离外周血单核细胞(PBMC),并使用 Quantitive Real-Time PCR 测量 HRH-1 和 HRH-4 mRNA 基因表达。我们从基础基因表达和 FXF 和组胺刺激后获得结果。
与对照组相比,过敏组 HRH-1 mRNA 基础基因表达明显更高,HRH-4 表达明显更低。在两组中,与未处理的细胞相比,组胺刺激后 HRH-1 mRNA 基因表达均观察到统计学上显著增加,而在 HRH-4 中仅在过敏组观察到统计学上的增加。FXF 依次阻断了组胺对 HRH-1 mRNA 基因表达的亲和力,但对 HRH-4 没有反应,我们没有观察到任何反应。
结果清楚地推翻了我们关于使用 FXF 阻断 HRH-4 过表达的可能性并为过敏疾病开辟新治疗途径的假设。