Saffitz J E
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.
Am J Physiol. 1989 Jul;257(1 Pt 2):H162-9. doi: 10.1152/ajpheart.1989.257.1.H162.
The physiological and pathophysiological roles of myocardial alpha 1-adrenergic receptors are not clearly defined. To delineate the distribution of alpha 1-receptors in myocytic and vascular components of the heart, we characterized the binding of [3H]prazosin to alpha 1-receptors in unfixed, transmural slices of feline left ventricle. Specific binding ratios greater than 95% were achieved at radioligand concentrations near the dissociation constant (Kd). Binding of radioligand to receptors in transmural slices was rapid, reversible, saturable, stereoselective, and displaceable by subtype-selective antagonists with a rank order of potency characteristic of alpha 1-receptors. Analysis of binding isotherms indicated a Bmax of 9.1 +/- 1.9 fmol/mg protein and a Kd of 36.9 +/- 6.3 pM. Results of light microscopic autoradiography indicated that regions composed of closely arranged cardiac myocytes contained three to fourfold more alpha 1-receptors per unit section area than the resistance microvasculature, which in turn contained approximately twice the density of alpha 1-receptors observed in the medial smooth muscle of large conductance arteries. No differences in the density of alpha 1-receptors between subepicardial and subendocardial regions were observed for either myocytic regions or coronary arterioles. These results indicate that myocytic regions of the cat ventricle contain a high density of alpha 1-adrenergic receptors. The methods developed should be of value in characterizing the distribution and function of alpha 1-receptors and mechanisms of regulation of adrenergic responsiveness in intact myocyardium.
心肌α1 - 肾上腺素能受体的生理和病理生理作用尚未明确界定。为了描绘α1受体在心脏肌细胞和血管成分中的分布，我们对[3H]哌唑嗪与猫左心室未固定的透壁切片中的α1受体结合进行了表征。在接近解离常数（Kd）的放射性配体浓度下，特异性结合率大于95%。放射性配体与透壁切片中受体的结合迅速、可逆、可饱和、具有立体选择性，并且可被亚型选择性拮抗剂取代，其效价顺序具有α1受体的特征。结合等温线分析表明，Bmax为9.1±1.9 fmol/mg蛋白质，Kd为36.9±6.3 pM。光学显微镜放射自显影结果表明，由紧密排列的心肌细胞组成的区域每单位截面积所含的α1受体比阻力微血管多三到四倍，而阻力微血管所含的α1受体密度又大约是大电导动脉中膜平滑肌的两倍。在心外膜下和心内膜下区域，无论是肌细胞区域还是冠状动脉小动脉，α1受体密度均未观察到差异。这些结果表明，猫心室的肌细胞区域含有高密度的α1 - 肾上腺素能受体。所开发的方法对于表征α1受体的分布和功能以及完整心肌中肾上腺素能反应性的调节机制应具有重要价值。
