Identification of higenamine as a novel α1‐adrenergic receptor antagonist. (15th January 2019)

• Record Type: Journal Article
• Authors: Zhang, Nana; Qu, Kai; Wang, Minjie; Yin, Qian; Wang, Wenjing; Xue, Lixiang; Fu, Haian; Zhu, Haibo; Li, Zijian
• Is Part Of: Phytotherapy research. Volume 33:Number 3(2019)
• Page Start: 708
• Page End: 717
• Publication Date: 2019-01-15
• Subjects: antagonism -- blood pressure -- higenamine hydrochloride -- vasorelaxation -- α1‐adrenoceptor; Materia medica, Vegetable -- Periodicals; Botany, Medical -- Periodicals; Medicinal plants -- Periodicals; Plant Extracts -- therapeutic use -- Periodicals; Plants, Medicinal -- Periodicals; 581.634
• DOI: 10.1002/ptr.6261
• Languages: English
• ISSNs: 0951-418X

Abstract

Abstract : The α1 ‐adrenoceptor (α1 ‐AR) antagonists are potential candidates for the treatment of blood pressure. Higenamine (HG) is a novel α1 ‐AR antagonist. In this study, we investigated the effects of HG in HEK293A cells transfected with α1A ‐, α1B ‐, and α1D ‐AR in vitro, rat mesenteric artery ex vivo, Wistar–Kyoto rats and spontaneously hypertensive rats in vivo. The radioligand binding assay showed that HG competitively inhibited the binding of [ 3 H]‐prazosin to α1 ‐AR in a concentration‐dependent manner. The affinities ( p Ki) of HG for the cloned α1A ‐, α1B ‐, and α1D ‐AR were 6.57, 6.48, and 6.35, respectively, indicating that HG displayed no selectivity for the three α1 ‐AR subtypes. In in vitro studies, HG was able to blunt inositol monophosphate production. It also displayed an inhibitory effect on the influx and entry of calcium ions and phosphorylation of extracellular signal‐regulated kinase 1 and 2 induced by phenylephrine (PE). In ex vivo studies, PE caused a dose‐dependent inotropic response curve, and the pA2 value for HG was 6.86 ± 0.29. In addition, the in vivo results showed that HG could decrease the blood pressure in normotension, spontaneous hypertension, and PE‐induced hypertension models. These results indicate that HG can directly bind to α1 ‐AR and it appears to be a novel antagonist for α1 ‐AR, which may contribute to its hypotensive effect.