Ferrante F, Cadoni A, Zaccheo D, Amenta F
Sezione di Anatomia Umana, Università di Camerino, Italy.
Clin Exp Hypertens. 1995 Aug;17(6):895-912. doi: 10.3109/10641969509033642.
The anatomical localization of Ca2+ channels of the L-type was analyzed in sections of the human right and anterior interventricular coronary arteries by using in vitro light microscope autoradiography associated with radioligand binding techniques. [3H]Nicardipine was utilised as a ligand. Binding of the radioligand to sections of the two coronary arteries was time-, temperature- and concentration-dependent. Analysis of binding isotherms revealed a dissociation constant value of about 0.5 nM in the two arteries and maximum binding capacities of 139 +/- 6.4 fmol/mg tissue for the right coronary artery and of 173 +/- 9.5 for the anterior interventricular branch. The pharmacological profile of [3H]nicardipine binding to sections of human coronary arteries was consistent with the labelling of Ca2+ channels of the L-type. Dihydropyridine derivatives were the most powerful competitors of [3H]nicardipine binding, whereas phenylalkylamines, benzothiazepine or non-selective channel modulators were weak competitors or ineffective. Light microscope autoradiography revealed the highest density of [3H]nicardipine binding sites in the tunica media of the coronary arteries. In this layer Ca2+ channels of the L-type are located within smooth muscle cells. A lower accumulation of the radioligand occurred in the tunica adventitia, whereas no specific binding was found in the tunica intima. Study of the localization of Ca2+ channels in sections of human coronary arteries may contribute to a better understanding of the mechanism of the marked coronary dilatory activity elicited by Ca2+ antagonists demonstrable in both in vitro preparations and in vivo.
运用与放射性配体结合技术相关的体外光学显微镜放射自显影术，对人右冠状动脉和前室间冠状动脉切片中L型钙通道的解剖定位进行了分析。使用[3H]尼卡地平作为配体。放射性配体与两条冠状动脉切片的结合呈时间、温度和浓度依赖性。结合等温线分析显示，两条动脉的解离常数约为0.5 nM，右冠状动脉的最大结合容量为139±6.4 fmol/mg组织，前室间支为173±9.5 fmol/mg组织。[3H]尼卡地平与人冠状动脉切片结合的药理学特征与L型钙通道的标记一致。二氢吡啶衍生物是[3H]尼卡地平结合的最强竞争者，而苯烷基胺、苯并噻氮䓬或非选择性通道调节剂是弱竞争者或无效。光学显微镜放射自显影显示冠状动脉中膜[3H]尼卡地平结合位点密度最高。在这一层中，L型钙通道位于平滑肌细胞内。放射性配体在外膜中的积累较少，而在内膜中未发现特异性结合。研究人冠状动脉切片中钙通道的定位可能有助于更好地理解钙拮抗剂在体外制剂和体内均能表现出的显著冠状动脉扩张活性的机制。
