Phosphodiesterase function and regulation

Postnatal Development Shapes the Cardiac Response to Milrinone

This study examines how postnatal development affects the cardiac response to milrinone in guinea pig hearts, finding age-dependent variations in chronotropic, inotropic, and lusitropic effects.

Uncovering a Sex-Specific cAMP Landscape in Vascular Smooth Muscle

This study identifies sex-specific cAMP signaling differences in vascular smooth muscle, showing female-specific SR cAMP pools and their hormonal regulation.

Comparative effects of central and peripheral PDE10A inhibition on weight gain following semaglutide cessation in diet-induced obese mice

This study compares the effects of central and peripheral PDE10A inhibition on weight gain after stopping semaglutide in obese mice, finding that central inhibition is more effective.

ADT-030, a novel PDE10 inhibitor, demonstrates potent antitumor activity in pancreatic ductal adenocarcinoma

Oral PDE10 inhibitor ADT-030 curbed KRAS-mutant pancreatic cancer growth and metastasis in mouse models, stayed active in KRAS-inhibitor-resistant cells, and shifted tumor immune profiles.

Subcellular pharmacology of a novel cell-permeable fluorescent phosphodiesterase inhibitor using advanced fluorescence microscopy

The paper develops a fluorescent PDE4 inhibitor to visualize drug-target interactions in living cells using advanced fluorescence microscopy techniques.

PKA can adopt structural or enzymatic roles depending on its anchoring site

This study shows that PKA can act as either an enzymatic or structural component depending on its anchoring site, using a SpyCatcher-SpyTag strategy to compare AKAP functions.

Reduced PDE4D expression and activity in Acrodysostosis Type 2 patient fibroblasts underlie disease pathology

This study shows reduced PDE4D expression and activity in ACRDYS2 patient fibroblasts, leading to altered cAMP/PKA signaling and compensatory changes in PDE4B.

Arteriolar GMP signaling revealed by FRET-based real-time measurement in vivo

This study uses FRET-based imaging to measure real-time cGMP levels in arterioles of live mice, showing PDEs affect signaling duration but not amplitude, and ACh does not induce endothelial NO release.

Molecular Determinants of Allosteric Inhibitor Affinity and Selectivity in PDE5

This study identifies molecular determinants of allosteric inhibitor affinity and selectivity in PDE5 by analyzing structural and thermodynamic factors.

Targeting phosphodiesterase 10A disrupts MAPK signaling pathways in the tumor microenvironment to unleash antitumor immunity

This study shows that PDE10A inhibition with ADT-030 suppresses tumor growth by disrupting MAPK signaling and enhancing antitumor immunity through immune cell modulation.

Precision Targeting of Troponin I Phosphorylation Prevents Diastolic Dysfunction while Preserving Systolic Performance

This paper identifies a nanodomain mechanism regulating troponin I phosphorylation and demonstrates a peptide that selectively enhances relaxation without compromising systolic function in heart failure.

Phosphodiesterase type 1 regulates adenosine 2A receptor-associated cAMP signaling at the plasma membrane to increase myocardial contractility

This study shows PDE1 regulates A2AR-associated cAMP signaling at the sarcolemma to enhance myocardial contractility in healthy and failing hearts.

PDE3A2 modRNA Fine-Tunes Nuclear cAMP Microdomains and Reverses Pathological Cardiac Hypertrophy

This study develops PDE3A2-modRNA to restore nuclear cAMP microdomain regulation, reversing pathological cardiac hypertrophy in a mouse model.

Molecular mechanisms regulating PDE11A4 age-related liquid-liquid phase separation and its reversal by selective PDE11A4-targeted small molecules in cells and brain

This study identifies molecular mechanisms regulating PDE11A4 liquid-liquid phase separation and shows that PDE11A inhibitors can reverse it in cells and brain.

Phosphodiesterase 3A modulators sensitize tumor cells to Bcl-xL and Bcl-2/Bcl-xL inhibitors

This study identifies PDE3A modulators that synergize with Bcl-xL and Bcl-2/Bcl-xL inhibitors to induce tumor regression in sarcoma models.

Preclinical Evaluation of P4B-2412 as Phosphodiesterase 4B Radioligand for Positron Emission Tomography Imaging

This study develops and evaluates [18F]P4B-2412 as a PET radioligand for imaging PDE4B, showing high binding, specificity, and metabolic stability in rodent models.

Regulation of intracellular cAMP levels in osteocytes by mechano-sensitive focal adhesion kinase via PDE8A

This study identifies FAK's role in regulating cAMP levels in osteocytes through PDE8A, showing FAK inhibition increases cAMP and downstream signaling.

Differential effects of PDE4A5 on cAMP-dependent forms of long-term potentiation

This study investigates how different PDE4A isoforms affect cAMP-dependent long-term potentiation (LTP), finding that PDE4A5 specifically impairs TBS-LTP through its unique N-terminus.

Inhibition of cAMP signaling prevents congenital heart defects counteracting oxidative stress in Pde2A deficient embryos

This study identifies molecular mechanisms and drug targets for congenital heart defects in Pde2A-deficient embryos by analyzing gene expression and testing cAMP and oxidative stress modulators.

Biologic that disrupts PDE11A4 homodimerization in hippocampus CA1 reverses age-related proteinopathies in PDE11A4 and cognitive decline of social memories

The paper shows that disrupting PDE11A4 homodimerization in hippocampal CA1 reverses age-related PDE11A4 accumulation and cognitive decline of social memory.

Radiosynthesis and preclinical evaluation of a carbon-11 labeled PDE7 inhibitor for PET neuroimaging

This paper develops and evaluates [11C]26, a PET probe for imaging PDE7 in the brain, showing promising in vitro performance and moderate specific binding in nonhuman primates.

cGMP signaling: probing antagonistic cyclic nucleotide platelet signals by modeling and experiment

The paper develops and validates a model of cGMP signaling and VASP phosphorylation in platelets using data-driven approaches and experimental validation.

Inhibition of phosphodiesterase - 10A by Papaverine protects human cortical neurons from quinolinic acid-induced oxidative stress and synaptic proteins alterations

This study shows that papaverine inhibits PDE10A, reducing oxidative stress and protecting synaptic proteins in human cortical neurons exposed to quinolinic acid.

Guanine-nucleotide Exchange Modulator, GIV/Girdin, Serves as a Tunable Valve for Growth Factor-Stimulated Cyclic AMP Signals

The paper presents a network-based model of GIV/Girdin-dependent cAMP signaling, revealing its role as a tunable control valve distinct from GPCRs and PDEs.