Cyclic nucleotide hydrolysis in bovine aortic endothelial cells in culture: Differential regulation in cobblestone and spindle phenotypes

Cyclic nucleotide phosphodiesterases (PDEs) were investigated in cultured b ovine aortic endothelial cells having two phenotypes, cobblestone and spind le, representing, respectively, the resting and angiogenic phenotypes in vi vo. Spindle cell homogenates displayed higher hydrolytic activities towards cAMP (52%) and cGMP (10-fold). These increases were due to: (1) increased number of spindle PDE isozymes in the cytosolic fraction (for cAMP: PDE1, P DE2, PDE3 and PDE4 compared to PDE2 and PDE4 in cobblestone; for cGMP: PDE2 and PDE5 compared to PDE2 in cobblestone); (2) increased spindle-specific activities of cytosolic and particulate PDE2, cytosolic PDES and particulat e PDE4. These changes were associated with an increase in spindle transcrip ts: 7.5 kb PDE3A (6-fold) and 7.0 kb PDE4D (3-fold). Moreover, cAMP hydroly sis in the two phenotypes was differently regulated by 5 mu M cGMP: 60% inc rease in total cAMP-PDE activity in cobblestone homogenate related to PDE2 stimulation; 30% decrease in spindle homogenate related to PDES inhibition. This underlines the roles played by PDE2, PDE3 and PDE5 in the cross-talk involving the two cyclic nucleotides, These changes in PDE isozyme expressi on along with the cross-talk between cAMP and cGMP may well modulate NO pro duction and consequently might participate in angiogenesis, making PDEs pot ential targets to modulate angiogenesis. Copyright (C) 2000 S. Karger AG, B asel.