Department of Internal Medicine , Faculty of Medicine , Kyoto University , Japan .
Prostaglandins 41 : 97-110 ( 1991)
Abstract
The effects of U-61,431F , ciprostene , a stable prostacyclin analogue , were examined on the proliferation of cultured quiescent bovine aortic endothelial cells ( EC ) and smooth muscle cells ( SMC ) .
After stimulation with 5% fetal calf serum , U-61,431F suppressed both the DNA synthesis and proliferation of SMC dose-dependently at the concentration of 3-100 microM , but had no effect on either of them in EC at a concentration of up to 30 microM .
The inhibitory effect on DNA synthesis was greater in SMC than in EC at 3-50 microM .
When SMC were stimulated with platelet-derived growth factor ( PDGF ) for 2 hrs followed by a 22-hr incubation with insulin , U-61,431F ( 1-50 microM ) administered at the time of PDGF stimulation did not inhibit DNA synthesis .
SMC initiated and terminated DNA synthesis at about 15-18 h and 24 h after stimulation with serum , respectively .
Inhibition of DNA synthesis in serum-stimulated SMC as a function of the addition time of U-61,431F reduced at 3-12 h after the stimulation .
U-61,431F raised the cyclic AMP ( cAMP ) content in SMC .
Moreover , a phosphodiesterase inhibitor , -isobutyl-1-methylxanthine , and a more specific cAMP phosphodiesterase inhibitor , Ro 20-1724 , augmented the inhibition of DNA synthesis in SMC concomitant with further elevation of cAMP level .
These results suggest that U-61,431F inhibits DNA synthesis of SMC acting in the progression stage rather than in the competence stage , with little antiproliferative effect on EC .
cAMP may play an important role in its antiproliferative action in SMC .