Histamine H1 and H2 receptor gene and protein levels are differentially expressed in the hearts of rodents and humans
Histamine H1 and H2 receptor gene and protein levels are differentially expressed in the hearts of rodents and humans
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DOI：
10.1124/jpet.103.063065
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发表时间：
2004-05-01
影响因子：
3.5
通讯作者：
Levi, R
中科院分区：
文献类型：
--
作者：
Matsuda, N;Jesmin, S;Levi, R
组胺是高度集中在动物和人类的心脏。在病理生理条件下过度释放，如速发型超敏反应和感染性休克，会导致心脏功能障碍和心律失常。先前的药理学研究表明，H-1和H-2受体介导这些作用。然而，心脏组胺受体的分布和分子特征的准确估计是缺失的。最近，编码H-1和H-2受体的基因已被克隆，氨基酸序列和蛋白质结构已被阐明。因此，我们分析了H-1和H-2受体在豚鼠、兔、大鼠和人类心脏的心房和心室中的基因和蛋白质表达水平。用免疫细胞化学技术，我们研究了H-1和H-2受体蛋白在豚鼠心脏的窦房结和房室结及周围心肌的区域表达。北方和Western印迹研究表明，心脏组胺H-1和H-2受体在不同哺乳动物物种和心脏的不同区域中分布不均匀，而H-2受体在人类心房和心室肌中大量表达。这些发现与先前的药理学研究一致，清楚地表明心脏对组胺的反应取决于H-1和H-2受体的表达水平。人类心脏中H-2受体的高丰度表达证实了组胺在各种疾病状态下的促组胺性。组胺受体亚型在人类心脏中的差异分布的新知识将促进更好地了解组胺在心血管病理生理学中的作用，并可能有助于组胺诱导的心脏功能障碍的新的治疗方法。
Histamine is highly concentrated in the heart of animals and humans. Excessive release in pathophysiological conditions, such as immediate hypersensitivity and septic shock, causes cardiac dysfunction and arrhythmias. Previous pharmacological studies revealed that H-1 and H-2 receptors mediate these effects. Yet, an accurate estimate of the distribution and molecular characteristics of cardiac histamine receptors is missing. Recently, the genes encoding H-1 and H-2 receptors have been cloned, and the amino acid sequence and protein structure have been elucidated. Accordingly, we analyzed gene and protein expression levels of H-1 and H-2 receptors in atria and ventricles of guinea pig, rabbit, rat, and human hearts. With immunocytochemical techniques, we examined the regional expression of H-1 and H-2 receptor proteins in the sinoatrial and atrioventricular nodes and surrounding myocardium of the guinea pig heart. Northern and Western blot studies revealed that cardiac histamine H-1 and H-2 receptors are variably distributed among different mammalian species and different regions of the heart, whereas H-2 receptors are abundantly expressed in human atrial and ventricular myocardium. These findings agree with those of previous pharmacological studies, clearly demonstrating that the responses of the heart to histamine depend on the expression level of H-1 and H-2 receptors. The highly abundant expression of H-2 receptors in the human heart substantiates histamine arrhythmogenicity in various disease states. The new knowledge of a differential distribution of histamine receptor subtypes in the human heart will foster a better understanding of histamine roles in cardiovascular pathophysiology and may contribute to new therapeutic approaches to histamine-induced cardiac dysfunctions.