Cyclic nucleotide-mediated regulation of vascular smooth muscle cell cyclic nucleotide phosphodiesterase activity. Selective effect of cyclic AMP

Cell Biochemistry and Biophysics
D H Maurice

Abstract

Cultured rat aortic vascular smooth muscle cells (VSMC) express both cGMP- inhibited cAMP phosphodiesterase (PDE-3) and Ro,20-1724-inhibited cAMP phosphodiesterase (PDE-4) activities. Utilizing a PDE-3-selective inhibitor (cilostamide) and a PDE-4-selective inhibitor (Ro,20-1724), PDE-3 and PDE-4 activities were shown to account for 15 and 55% of total VSMC cAMP phosphodiesterase (PDE) activity. Incubations of VSMC with either forskolin or 8-bromo-cAMP caused a concentration- and time-dependent increase in total cellular cAMP PDE activity. In these cells, both PDE-3 and PDE-4 activities were increased, with a relatively larger effect observed on PDE-3 activity. Similar incubations with an activator of soluble guanylyl cyclase (sodium nitroprusside) or with 8-bromo-cGMP did not increase cAMP PDE activity. cAMP-induced increases in cAMP PDE activity were inhibited with actinomycin D or cycloheximide, demonstrating that new mRNA and protein synthesis were required. We conclude that VSMC cAMP PDE activity is elevated following long-term elevation of cAMP, and that increases in PDE-3 and PDE-4 activities account for more than 70% of this increase. These results may have implications for long-term use of cAMP PDE inhibitors as therap...Continue Reading

References

Apr 1, 1992·Canadian Journal of Physiology and Pharmacology·S C Pang, S L Venance
Jan 10, 1991·European Journal of Pharmacology·D H MauriceR J Haslam
Apr 1, 1990·Trends in Pharmacological Sciences·J A Beavo, D H Reifsnyder
Dec 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·P G GrantR W Colman
Nov 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·J V SwinnenM Conti
Jul 1, 1995·Cellular Signalling·V C ManganielloP Belfrage

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