Platelets contain two cAMP phosphodiesterases (PDEs) which regulate intracellular cAMP levels, cGMP-inhibited cAMP PDE (PDE3A) and cGMP-stimulated PDE (PDE2A). Using the PDE3 inhibitor, milrinone and the PDE2 inhibitor, erythro-9-(2-hydroxyl-3-nonyl)adenine (EHNA), we have explored the contribution of each PDE to the regulation of platelet function. Inhibition of PDE2 resulted in higher levels ...

Cyclic nucleotide phosphodiesterases (PDEs) are a superfamily of enzymes whose physiological role is the attenuation of the signaling mediated by the ubiquitous second messengers cAMP and cGMP. Given the myriad of physiological processes regulated by cAMP and cGMP, PDEs have long been studied as potential therapeutic targets. Although phosphodiesterase 3 (PDE3) activity is abundant in human car...

We are studying a Turkish family with autosomal-dominant hypertension and brachydactyly; affected persons die of stroke before 50 years of age. With interphase fluorescence in situ hybridization, we found a chromosome 12p deletion, reinsertion, and inversion in affected persons. This finding suggested that the hypertension could be caused by one or more of 3 genes, the ATP-dependent potassium c...

Cyclic nucleotide phosphodiesterases (PDEs) are a superfamily of enzymes whose physiological role is the attenuation of the signaling mediated by the ubiquitous second messengers cAMP and cGMP. Given the myriad of physiological processes regulated by cAMP and cGMP, PDEs have long been studied as potential therapeutic targets. Although phosphodiesterase 3 (PDE3) activity is abundant in human car...

NEW INSIGHTS FROM THE STRUCTURE FUNCTION ANALYSIS OF THE CATALYTIC REGION OF HUMAN PLATELET PDE3A: A ROLE FOR THE UNIQUE 44 AMINO ACID INSERT Su-Hwi Hung*, Wei Zhang*, Robin A. Pixley, Bradford A. Jameson, Yu Chu Huang, Roberta F. Colman and Robert W. Colman From the Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia PA, Department of Biochemistry, Drexel ...

β-adrenergic signaling pathways mediate key aspects of cardiac function. Its dysregulation is associated with a range of cardiac diseases, including dilated cardiomyopathy (DCM). Previously, we established an iPSC model of familial DCM from patients with a mutation in TNNT2, a sarcomeric protein. Here, we found that the β-adrenergic agonist isoproterenol induced mature β-adrenergic signaling in...

Abstract Thrombospondin-1 (TSP-1) is released by platelets upon activation and can increase platelet activation, but its role in hemostasis vivo unclear. We show that TSP-1 a critical mediator of promotes modulating inhibitory cyclic adenosine monophosphate (cAMP) signaling. Genetic deletion did not affect vitro, models thrombosis showed TSP-1–deficient mice had prolonged bleeding, defective th...

Many studies have shown that cyclic adenosine-5'-monophosphate (cAMP)-dependent protein kinase A (PKA) and G-protein-coupled receptor 3 (GPR3) are crucial for controlling meiotic arrest in oocytes. However, it is unclear how gonadotropins modulate these factors to regulate oocyte maturation, especially by gap junctional communication (GJC). Using an in vitro meiosis-arrested mouse cumulus-oocyt...

OBJECTIVE • To investigate the regulatory role of androgen in VIP-mediated erectile effect. Androgen is essential for physiological erection. Vasoactive intestinal polypeptide (VIP) is an important erectile neurotransmitter. While previous studies demonstrated that VIP expression in the penis was androgen-independent, it remains controversial whether androgen has any effect on VIP-mediated erec...