Inhibition of cAMP-phosphodiesterase 4 (PDE4) potentiates the anesthetic effects of Isoflurane in mice

2021 ◽  
Vol 186 ◽  
pp. 114477
Author(s):  
Ileana V. Aragon ◽  
Abigail Boyd ◽  
Lina Abou Saleh ◽  
Justin Rich ◽  
Will McDonough ◽  
...  
Keyword(s):  
Camp Phosphodiesterase ◽  
Phosphodiesterase 4

Prolonged heterologous β2-adrenoceptor desensitization promotes proasthmatic airway smooth muscle function via PKA/ERK1/2-mediated phosphodiesterase-4 induction

2008 ◽  
Vol 294 (6) ◽  
pp. L1055-L1067 ◽  
Author(s):  
Aihua Hu ◽  
Gustavo Nino ◽  
Judith S. Grunstein ◽  
Sumbul Fatma ◽  
Michael M. Grunstein
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Intracellular Signaling ◽  
Prolonged Exposure ◽  
Pde4 Inhibitor ◽  
Prostaglandin E ◽  
Protein Signaling ◽  
Camp Phosphodiesterase ◽  
Phosphodiesterase 4 ◽  
Β2 Adrenergic Receptor

β2-Adrenergic receptor (β2AR) agonists acutely relieve bronchoconstriction via cAMP-mediated relaxation of airway smooth muscle (ASM). Airway constrictor responsiveness may be significantly heightened, however, following protracted exposure to these agents, presumably reflecting the effects of β2AR desensitization in ASM accompanying prolonged cAMP signaling. Because cAMP phosphodiesterase (PDE) activity can significantly modulate ASM contractility, we investigated the mechanism regulating PDE expression and its potential role in mediating changes in agonist-induced constrictor and relaxation responsiveness in ASM following its heterologous β2AR desensitization by prolonged exposure to cAMP-elevating agents. Isolated rabbit ASM tissues and cultured human ASM cells treated for 24 h with the receptor- or nonreceptor-coupled cAMP-stimulating agent, prostaglandin E2 (PGE2) or forskolin, respectively, exhibited constrictor hyperresponsiveness to acetylcholine and impaired β2AR-mediated relaxation and cAMP accumulation. These proasthmatic-like changes in ASM function were associated with upregulated PDE4 activity, reflective of increased transcription of the PDE4D5 isoform, and were prevented by pretreatment of the ASM with a PDE4 inhibitor. Extended studies using gene silencing and pharmacological approaches to inhibit specific intracellular signaling molecules demonstrated that the mechanism underlying PGE2-induced transcriptional upregulation of PDE4D5 involves PKA-dependent activation of Gi protein signaling via the βγ-subunits, the latter eliciting downstream activation of ERK1/2 and its consequent induction of PDE4D5 transcription. Collectively, these findings identify that β2AR desensitization in ASM following prolonged exposure to cAMP-elevating agents is associated with proasthmatic-like changes in ASM responsiveness that are mediated by upregulated PDE4 expression induced by activated cross talk between the PKA and ERK1/2 signaling pathways.

PDE4B5, a Novel, Super-Short, Brain-Specific cAMP Phosphodiesterase-4 Variant Whose Isoform-Specifying N-Terminal Region Is Identical to That of cAMP Phosphodiesterase-4D6 (PDE4D6)

2007 ◽  
Vol 322 (2) ◽  
pp. 600-609 ◽  
Author(s):  
York-Fong Cheung ◽  
Zhengyan Kan ◽  
Philip Garrett-Engele ◽  
Irene Gall ◽  
Hannah Murdoch ◽  
...  
Keyword(s):  
Terminal Region ◽  
Camp Phosphodiesterase ◽  
Phosphodiesterase 4

Inhibitors of blood platelet cAMP phosphodiesterase. 4. Structural variation of the side-chain terminus of water-soluble 1,3-dihydro-2H-imidazo[4,5-b]quinolin-2-one derivatives

1993 ◽  
Vol 36 (22) ◽  
pp. 3251-3264 ◽  
Author(s):  
Nicholas A. Meanwell ◽  
Piyasena Hewawasam ◽  
Jeanine A. Thomas ◽  
J. J. Kim Wright ◽  
John W. Russell ◽  
...  
Keyword(s):  
Structural Variation ◽  
Blood Platelet ◽  
Water Soluble ◽  
Side Chain ◽  
Camp Phosphodiesterase ◽  
Phosphodiesterase 4

scholarly journals PAN‐selective inhibition of cAMP‐phosphodiesterase 4 (PDE4) induces gastroparesis in mice

2020 ◽  
Vol 34 (9) ◽  
pp. 12533-12548
Author(s):  
Will McDonough ◽  
Ileana V. Aragon ◽  
Justin Rich ◽  
James M. Murphy ◽  
Lina Abou Saleh ◽  
...  
Keyword(s):  
Selective Inhibition ◽  
Camp Phosphodiesterase ◽  
Phosphodiesterase 4

scholarly journals Dimerization of cAMP phosphodiesterase-4 (PDE4) in living cells requires interfaces located in both the UCR1 and catalytic unit domains

2015 ◽  
Vol 27 (4) ◽  
pp. 756-769 ◽  
Author(s):  
Graeme B. Bolger ◽  
Allan J. Dunlop ◽  
Dong Meng ◽  
Jon P. Day ◽  
Enno Klussmann ◽  
...  
Keyword(s):  
Living Cells ◽  
Camp Phosphodiesterase ◽  
Phosphodiesterase 4 ◽  
Catalytic Unit
Sign in / Sign up

Export Citation Format

Share Document