Clonidine stimulates force of contraction via histamine H2 receptors in the human atrium

Author:

Neumann Joachim1,Pockes Steffen2,Humphrys Laura J.2,Mönnich Denise2,Forster Lisa2,Kirchhefer Uwe3,Hofmann Britt4,Gergs Ulrich1

Affiliation:

1. Martin-Luther-University Halle-Wittenberg

2. University of Regensburg

3. University Hospital Münster, Westfälische Wilhelms-University

4. University Hospital Halle

Abstract

Abstract Introduction: Clonidine has various clinical effects mediated by agonism of α1- or α2-adrenoceptors and the blocking of HCN-channels. It is unknown whether clonidine can also stimulate human cardiac histamine H2 receptors (hH2R). Methods: We used isolated electrically stimulated left and spontaneously beating right atrial preparations from mice overexpressing the h H2R specifically in the heart (H2-TG), and spontaneously beating right atrial preparations of guinea pigs for comparison. Moreover, we studied isolated electrically stimulated muscle strips from the human right atrium. Results: Clonidine (1, 3, 10 µM) increased force of contraction in isolated left atrial preparations from H2-TG mice. In contrast, clonidine reduced the spontaneous beating rate in right atrial preparations from H2-TG. Clonidine raised the beating rate in guinea pig right atrial preparations. Clonidine failed to increase the force of contraction but reduced beating rate in wild type litter mate mice (WT). In WT, histamine failed to increase the force of contraction in left atrial preparations and beating rate in right atrial preparations. Clonidine (10 µM) increased the force of contraction in isolated human right atrial preparations. These effects in the human atrium were attenuated by cimetidine (10 µM). Clonidine increased the beating rate of the isolated spontaneously beating guinea pig right atrium and acted as a H2R partial agonist. Furthermore, clonidine showed binding to the guinea pig H2R (100 µM) using HEK cells in a recombinant expression system (pKi < 4.5) but not to the human H2R. Conclusions: These data suggest that clonidine can activate cardiac human histamine H2 receptors.

Publisher

Research Square Platform LLC

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3