Angiopeptin inhibits thymidine incorporation by explants of porcine coronary arteries.
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.
Vargas
R
R
Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, DC 20007, USA.
Wroblewska
B
B
Rego
A
A
Cathapermal
S
S
Ramwell
P W
PW
D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D000242:Cyclic AMP / Q000032:analysis; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology*; D010456:Peptides, Cyclic; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D013552:Swine; D013936:Thymidine / Q000378:metabolism*
D002317:Cardiovascular Agents; D009842:Oligopeptides; D010456:Peptides, Cyclic; C060347:lanreotide; D005576:Colforsin; D013004:Somatostatin; D000242:Cyclic AMP; D013936:Thymidine