Vargas R, Wroblewska B, Rego A, Cathapermal S, Ramwell P W
Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, DC 20007, USA.
J Cardiovasc Pharmacol. 1997 Feb;29(2):278-83. doi: 10.1097/00005344-199702000-00018.
Angiopeptin, a stable octapeptide analog of somatostatin, inhibits proliferation in a variety of cancer cell lines. We studied the effect of angiopeptin on 3H-thymidine uptake into ring segments from the porcine coronary tree. The incorporation of 3H-thymidine into segments of porcine left anterior descending (LAD) coronary artery was time dependent and reached a plateau after 48 h. The addition of angiopeptin (48.1 and 96.2 nM) to the culture medium significantly inhibited 3H-thymidine incorporation into the segments by 36.7 +/- 10.1% and 48.3 +/- 2.3% of the control, respectively. Forskolin (100 microM), inhibited 3H-thymidine incorporation (52.7 +/- 10.1%) to the same degree as did angiopeptin (96.2 nM). Incubation of the segments with 125I-labeled angiopeptin, for 2 h at 37 degrees C, showed angiopeptin uptake to be time dependent and exhibited a first-order kinetics, reaching equilibrium after 30 min. Autoradiographic studies showed a uniform distribution of angiopeptin within the endothelium, media, and adventitia. Most of the labeling was associated with the nuclei of the cells. Angiopeptin, after 30-min incubation, did not significantly modify the basal levels of cyclic adenosine monophosphate (cAMP). In contrast, forskolin (100 microM) elicited a 50-fold increase of the basal levels of cAMP. These results indicate that in addition to its endocrine effects, angiopeptin reduces the rate of proliferation by acting directly on the vessel wall.
血管肽素是一种稳定的生长抑素八肽类似物，可抑制多种癌细胞系的增殖。我们研究了血管肽素对猪冠状动脉环段摄取³H-胸腺嘧啶核苷的影响。³H-胸腺嘧啶核苷掺入猪左前降支（LAD）冠状动脉段的过程呈时间依赖性，48小时后达到平台期。向培养基中添加血管肽素（48.1和96.2 nM）可分别显著抑制³H-胸腺嘧啶核苷掺入段，抑制率分别为对照组的36.7±10.1%和48.3±2.3%。福斯高林（100 μM）抑制³H-胸腺嘧啶核苷掺入的程度（52.7±10.1%）与血管肽素（96.2 nM）相同。在37℃下将段与¹²⁵I标记的血管肽素孵育2小时，结果显示血管肽素的摄取呈时间依赖性，并呈现一级动力学，30分钟后达到平衡。放射自显影研究表明血管肽素在内皮、中膜和外膜内分布均匀。大部分标记与细胞核相关。孵育30分钟后，血管肽素并未显著改变环磷酸腺苷（cAMP）的基础水平。相比之下，福斯高林（100 μM）可使cAMP基础水平升高50倍。这些结果表明，除了其内分泌作用外，血管肽素还通过直接作用于血管壁来降低增殖速率。
