Activation and induction of cyclic AMP phosphodiesterase (PDE4) in rat pulmonary microvascular endothelial cells

Biochemical Pharmacology
Bing ZhuSamuel J Strada

Abstract

Regulation of the rolipram-sensitive cAMP-specific phosphodiesterase 4 (PDE4) gene family was studied in rat pulmonary microvascular endothelial cells (RPMVECs). Total PDE4 hydrolysis was increased within 10 min after addition of forskolin (10 microM), reached a maximum at 20-40 min, and then gradually declined in the cells. A similar activation of PDE4 activity was observed using a protein kinase A (PKA) activator, N(6)-monobutyryl cAMP. Both the forskolin and the N(6)-monobutyryl cAMP activated PDE4 activities were blocked by the PKA-specific inhibitor, H89. This forskolin-stimulated and PKA-mediated short-term activation of PDE4 activity was further confirmed by in vitro phosphorylation of 87kDa PDE4A6 and 83kDa PDE4B3 polypeptides using exogenous PKA Calpha. Increased immunoreactivity of phosphorylated PDE4A6 in situ was detected in Western blots by a PDE4A-phospho antibody specific to the putative PKA phosphorylation sites. Following long-term treatment of RPMVECs with rolipram and forskolin medium (RFM) for more than 60 days, PDE4 activity reached ten-fold higher values than control RPMVECS with twenty-fold increases detected in intracellular cAMP content. The RFM cells showed increased immunoreactivities of the constitut...Continue Reading

References

Nov 1, 1992·In Vitro Cellular & Developmental Biology : Journal of the Tissue Culture Association·P J Del VecchioA B Malik
May 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·J ColicelliM Wigler
Jul 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·J V SwinnenM Conti
Feb 26, 1998·American Journal of Respiratory and Critical Care Medicine·T J Torphy
Jun 25, 1998·The American Journal of Physiology·R H AdamsonF E Curry
Feb 17, 1999·Journal of Molecular and Cellular Cardiology·C C Michel
Jun 4, 1999·Trends in Cell Biology·M Colledge, J D Scott
Jul 17, 1999·The American Journal of Physiology·T StevensW J Thompson
Mar 14, 2000·Current Opinion in Cell Biology·S H Soderling, J A Beavo
Apr 6, 2000·American Journal of Physiology. Heart and Circulatory Physiology·P HeF E Curry
Sep 29, 2000·Progress in Nucleic Acid Research and Molecular Biology·S H FrancisJ D Corbin
Oct 26, 2002·Science·Stephen J PerryRobert J Lefkowitz
Dec 10, 2002·American Journal of Physiology. Lung Cellular and Molecular Physiology·Judy R CreightonTroy Stevens
Dec 21, 2002·The Journal of Biological Chemistry·Marco ContiCatherine Jin

❮ Previous
Next ❯

Citations

Nov 26, 2011·American Journal of Physiology. Cell Physiology·Wei P FeinsteinThomas C Rich
May 17, 2011·American Journal of Physiology. Lung Cellular and Molecular Physiology·Otgonchimeg RentsendorjDavid B Pearse
Jul 20, 2010·American Journal of Physiology. Lung Cellular and Molecular Physiology·Bing ZhuTroy Stevens
Jan 30, 2007·Respiratory Research·Ralph T SchermulyFrank Rose
Nov 1, 2011·Current Opinion in Pharmacology·Donald H Maurice
Apr 27, 2012·Journal of Neuroscience Research·C M AtkinsW D Dietrich
Mar 29, 2005·American Journal of Physiology. Lung Cellular and Molecular Physiology·Bing ZhuTroy Stevens
Jan 29, 2008·American Journal of Physiology. Lung Cellular and Molecular Physiology·Jeffrey M Dodd-oDavid B Pearse
Jul 24, 2015·American Journal of Physiology. Cell Physiology·Wenkuan XinThomas C Rich

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adrenergic Receptors: Trafficking

Adrenergic receptor trafficking is an active physiological process where adrenergic receptors are relocated from one region of the cell to another or from one type of cell to another. Discover the latest research on adrenergic receptor trafficking here.