人房室传导系统和心肌中内皮素受体亚型的特征与定位
Characterization and localization of endothelin receptor subtypes in the human atrioventricular conducting system and myocardium.
作者信息
Molenaar P, O'Reilly G, Sharkey A, Kuc R E, Harding D P, Plumpton C, Gresham G A, Davenport A P
机构信息
Department of Obstetrics and Gynaecology, Addenbrooke's Hospital, Cambridge, UK.
出版信息
Circ Res. 1993 Mar;72(3):526-38. doi: 10.1161/01.res.72.3.526.
The characterization and localization of endothelin A (ETA) and endothelin B (ETB) receptors have been determined in tissue sections of the human atrioventricular conducting system, surrounding regions of atrial and ventricular myocardium, and the left ventricular free wall by use of radioligand binding, polymerase chain reaction, and in situ hybridization. Selective ETA (BQ123) and ETB (BQ3020) compounds in conjunction with [125I]endothelin-1 revealed the presence of ETA and ETB receptors in the left ventricular free wall (BQ123: 57 +/- 5% ETA, 43 +/- 2% ETB, n = 3; BQ3020: 67 +/- 3% ETA, 33 +/- 3% ETB, n = 3). Autoradiography using [125I]endothelin-1 in the absence or presence of BQ3020, BQ123, or endothelin-1 showed ETA and ETB receptors localized to atrial and ventricular myocardium, the atrioventricular conducting system, and endocardial cells. There was a higher proportion of ETB receptors in the atrioventricular node and the penetrating and branching bundles of His than in the surrounding interventricular and interatrial septa (p < 0.0001). There was a lower density of ETB receptors in the interventricular septum compared with the interatrial septum and the atrioventricular conducting system (p = 0.009) and a lower density of ETA receptors in the atrioventricular conducting system compared with interatrial and interventricular septa (p = 0.008). Isolated right atrial myocytes showed a higher proportion of ETA receptors (91 +/- 12%, n = 3). Amplification of left ventricular free wall cDNA by polymerase chain reaction revealed the presence of ETA and ETB receptor mRNA. mRNA for both subtypes was detected in isolated atrial myocytes. In situ hybridization showed ETA and ETB receptor mRNA localization to atrial and ventricular myocardium, the atrioventricular conducting system, and endocardial cells. These studies demonstrate the presence of ETA and ETB receptors in human myocardium and the atrioventricular conducting system.
通过放射性配体结合、聚合酶链反应和原位杂交技术，已在人类房室传导系统、心房和心室心肌周围区域以及左心室游离壁的组织切片中确定了内皮素A（ETA）和内皮素B（ETB）受体的特征和定位。选择性ETA（BQ123）和ETB（BQ3020）化合物与[125I]内皮素-1结合显示，左心室游离壁中存在ETA和ETB受体（BQ123：57±5% ETA，43±2% ETB，n = 3；BQ3020：67±3% ETA，33±3% ETB，n = 3）。在不存在或存在BQ3020、BQ123或内皮素-1的情况下，使用[125I]内皮素-1进行放射自显影显示，ETA和ETB受体定位于心房和心室心肌、房室传导系统以及心内膜细胞。房室结以及希氏束的穿入和分支束中ETB受体的比例高于周围的室间隔和房间隔（p < 0.0001）。与房间隔和房室传导系统相比，室间隔中ETB受体的密度较低（p = 0.009），与房间隔和室间隔相比，房室传导系统中ETA受体的密度较低（p = 0.008）。分离的右心房肌细胞显示ETA受体的比例较高（91±12%，n = 3）。通过聚合酶链反应扩增左心室游离壁cDNA显示存在ETA和ETB受体mRNA。在分离的心房肌细胞中检测到两种亚型的mRNA。原位杂交显示ETA和ETB受体mRNA定位于心房和心室心肌、房室传导系统以及心内膜细胞。这些研究证明了人类心肌和房室传导系统中存在ETA和ETB受体。
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