Rasmussen R P, Minobe W, Bristow M R
Division of Cardiology, University of Utah School of Medicine, Salt Lake City 84132.
Biochem Pharmacol. 1990 Feb 15;39(4):691-6. doi: 10.1016/0006-2952(90)90147-d.
Studies in myopathic hamsters have described an increase in calcium antagonist binding sites, which is presumably associated with an increase in the number of calcium channels. Such an abnormality might predispose the heart to further myocardial damage from calcium overload. We tested the hypothesis that calcium antagonist binding sites are increased in human idiopathic dilated cardiomyopathy by examining [3H]PN 200-110 and [3H]nitrendipine binding in membranes prepared from nonfailing controls and severely failing ventricles with idiopathic dilated cardiomyopathy. Despite the fact that beta receptor density was decreased by 50% in failing hearts (iodocyanopindolol Bmax 84.4 +/- 8.9 fmol/mg protein in nonfailing hearts vs 42.9 +/- 3.2 fmol/mg in failing hearts, P less than 0.01), dihydropyridine calcium antagonist binding sites were not reduced significantly by heart failure. Maximum binding of [3H]PN 200-110 was 92.9 +/- 19.4 fmol/mg protein in membranes derived from failing ventricles, and 93.5 +/- 17.4 fmol/mg in membranes derived from nonfailing ventricles (P = NS); values for [3H]nitrendipine maximum binding were similar to those for [3H]PN 200-110 and also were not reduced significantly in failing ventricles. Additionally, the dissociation constants (KD) for [3H]nitrendipine and [3H]PN 200-110 were not significantly different in failing and nonfailing heart. We conclude that dihydropyridine calcium antagonist binding sites are not altered significantly in the failing human left ventricle with idiopathic dilated cardiomyopathy.
对患肌病仓鼠的研究表明，钙拮抗剂结合位点有所增加，这可能与钙通道数量的增加有关。这种异常情况可能使心脏更容易因钙超载而受到进一步的心肌损伤。我们通过检测[3H]PN 200 - 110和[3H]尼群地平在由非衰竭对照组以及患有特发性扩张型心肌病的严重衰竭心室制备的膜中的结合情况，来验证特发性扩张型心肌病患者的钙拮抗剂结合位点是否增加这一假设。尽管衰竭心脏中的β受体密度降低了50%（非衰竭心脏中碘氰吲哚洛尔的Bmax为84.4±8.9 fmol/mg蛋白质，而衰竭心脏中为42.9±3.2 fmol/mg，P<0.01），但二氢吡啶钙拮抗剂结合位点并未因心力衰竭而显著减少。[3H]PN 200 - 110在衰竭心室来源的膜中的最大结合量为92.9±19.4 fmol/mg蛋白质，在非衰竭心室来源的膜中为93.5±17.4 fmol/mg蛋白质（P = 无显著差异）；[3H]尼群地平的最大结合量值与[3H]PN 200 - 110相似，在衰竭心室中也未显著降低。此外，[3H]尼群地平和[3H]PN 200 - 110在衰竭和非衰竭心脏中的解离常数（KD）没有显著差异。我们得出结论，在患有特发性扩张型心肌病的衰竭人类左心室中，二氢吡啶钙拮抗剂结合位点没有显著改变。
