β_2-肾上腺素受体在新生大鼠心肌成纤维细胞中的分布及其促增殖作用  

Expression of β_2-adrenergic receptor and its effect on the proliferation of neonatal rat cardiac fibroblasts

作　　者：尹峰[1] 吕志珍[1] 韩启德[1] 张幼怡[1] 

机构地区：[1]北京大学第三医院血管医学研究所,分子心血管学教育部重点实验室,北京100083

出　　处：《生理学报》2003年第3期251-254,共4页Acta Physiologica Sinica

基　　金：ThisworkwassupportedbytheNationalBasicResearchPrioritiesProgrammeofChina (G2 0 0 0 0 5 690 6)andtheNationalNaturalScienceFoundationofChina (No 30 0 70 872 )

摘　　要：为了明确 β 肾上腺素受体 (AR)亚型在新生大鼠心肌成纤维细胞中的分布及其在成纤维细胞增殖反应中的作用 ,采用放射配体结合实验和 [3H] thymidine掺入法检测了新生大鼠心肌成纤维细胞的 β AR密度和DNA合成速率。结果显示 ,在培养心肌细胞和心肌成纤维细胞中 β AR密度 (Bmax)和解离常数 (KD)无显著性差异 ;竞争抑制曲线分析结果提示 ,心肌成纤维细胞对CGP 2 0 712A和ICI 1185 5 1单位点拟合均显著优于两位点拟合 (P <0 0 1) ,表现为对选择性 β1 AR拮抗剂CGP 2 0 712A的低亲和性 (IC50 值 :10 1μmol/L)和对选择性 β2 AR拮抗剂ICI 1185 5 1的高亲和性(IC50 值 :0 147μmol/L)。异丙肾上腺素 (ISO)促心肌成纤维细胞增殖作用可被ICI1185 5 1和心得安 (非选择性 β AR拮抗剂 )完全抑制 ,而CGP 2 0 712A则无此作用。上述结果提示 ,在培养心肌成纤维细胞中β2 AR亚型占绝对优势 ,并且ISO引起的心肌成纤维细胞增殖反应是由 β2The expression of β-adrenergic receptor subtypes and its effect on neonatal rat cardiac fibroblast proliferation were investigated by radioligand binding assay and [ 3H]-thymidine incorporation analysis, respectively. The results indicated that there was no significant difference in the β-adrenergic receptor density (B max) and affinity (K D) between cardiomyocytes and cardiac fibroblasts. The [ 125I]-pindolol competitive inhibition curves (ICI 118551 and CGP 20712A) were significantly better fit in a one-site model in membrane preparation of cardiac fibroblasts. In cultured cardiac fibroblasts, 0.1 μmol/L isoproterenol-induced [ 3H]-thymidine incorporation was completely inhibited by a selective β 2-AR antagonist ICI 118551, or a non-selective β-AR antagonist propranolol, but not by CGP 20712A, a selective β 1-AR antagonist. These results suggest that isoproterenol-induced cardiac fibroblast proliferation is mediated by β 2-AR, the preponderant β-AR subtype in cardiac fibroblasts.

关 键 词：Β-肾上腺素受体 放射配体结合实验 心肌成纤维细胞 增殖 

分 类 号：R541[医药卫生—心血管疾病]