ANGIOPEPTIN INHIBITS THYMIDINE INCORPORATION BY EXPLANTS OF PORCINE CORONARY-ARTERIES

Angiopeptin, a stable octapeptide analog of somatostatin, inhibits pro liferation in a variety of cancer cell lines. We studied the effect of angiopeptin on H-3-thymidine uptake into ring segments from the porci ne coronary tree. The incorporation of H-3-thymidine into segments of porcine left anterior descending (LAD) coronary artery was time depend ent and reached a plateau after 48 h. The addition of angiopeptin (48. 1 and 96.2 nM) to the culture medium significantly inhibited 3H-thymid ine incorporation into the segments by 36.7 +/- 10.1% and 48.3 +/- 2.3 % of the control, respectively. Forskolin (100 mu M), inhibited H-3-th ymidine incorporation (52.7 +/- 10.1%) to the same degree as did angio peptin (96.2 nM). Incubation of the segments with I-125-labeled angiop eptin, for 2 h at 37 degrees C, showed angiopeptin uptake to be time d ependent and exhibited a first-order kinetics, reaching equilibrium af ter 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, af ter 30-min incubation, did not significantly modify the basal levels o f cyclic adenosine monophosphate (cAMP). In contrast, forskolin (100 m u M) elicited a 50-fold increase of the basal levels of cAMP. These re sults indicate that in addition to its endocrine effects, angiopeptin reduces the rate of proliferation by acting directly on the vessel wal l.