Gastrointestinal stromal tumors, which are thought to derive from interstitial cells of Cajal or their precursors, often harbor an oncogenic mutation of the KIT receptor tyrosine kinase. Sprouty homolog 4, a known negative regulator of ERK pathway, has been identified in the interstitial cells of Cajal in the KitK641E murine model of gastrointestinal stromal tumors. Sprouty homolog 4 was upregu...

In isolated superior mesenteric artery rings from age-matched control rats and streptozotocin (STZ)-induced diabetic rats, we investigated the role of cAMP in endothelium-derived hyperpolarizing factor (EDHF)-type relaxation. The ACh-induced EDHF-type relaxation was significantly weaker in STZ-induced diabetic rats than in control rats, and in both groups of rats it was attenuated by 18alpha-gl...

How does the follicle coordinate meiosis progression? The ovarian follicle is an integrated system in which follicular cells regulate oocyte progression into meiosis. Oocytes are large cells that divide asymmetrically to preserve stores for future embryonic development. To do this, they must coordinate asymmetric spindle positioning with cell cycle progression and chromosome segregation. In mam...

Cyclic AMP (cAMP) plays a critical role in oocyte meiotic maturation. However, the source of cAMP surge prior to maturation and the direction of gap junction-dependent cAMP movement are unclear. In this study, inhibition of gap junctional communication (GJC) using carbenoxolone (3.5 h) induced meiotic resumption in ~90% of follicle-enclosed oocytes (FEOs). The concentration of cAMP in a single ...

During mammalian oocyte growth, genomic DNA may accumulate DNA double-strand breaks (DSBs) induced by factors such as reactive oxygen species. Recent evidence demonstrated that slight DSBs do not activate DNA damage checkpoint proteins in denuded oocytes. These oocytes, even with DNA DSBs, can resume meiosis and progress to metaphase of meiosis II. Meiotic resumption in oocytes is also controll...

Chronic heart failure (HF) is a leading cause of morbidity and mortality worldwide. One important cause of HF is persistant arterial hypertension. Given the poor clinical prognosis, understanding the mechanisms preventing or driving hypertensive cardiac hypertrophy and the transition to failure is a major focus of research in cardiovascular medicine. In this issue, Perera et al provide new evid...

Phosphodiesterase 3 (PDE3) and PDE4 regulate levels of cyclic AMP, which are critical in various cell types involved in allergic airway inflammation. Although PDE4 inhibition attenuates allergic airway inflammation, reported side effects preclude its application as an antiasthma drug in humans. Case reports showed that enoximone, which is a smooth muscle relaxant that inhibits PDE3, is benefici...

The squamous cell carcinoma HeLa cell line and an epithelial cell line hTERT-RPE with a nonmalignant phenotype were interrogated for HeLa cell selectivity in response to 1267 annotated compounds representing 56 pharmacological classes. Selective cytotoxic activity was observed for 14 of these compounds dominated by cyclic adenosine monophosphate (cAMP) selective phosphodiesterase (PDE) inhibito...

Smooth muscle of the gut undergoes rhythmic cycles of contraction and relaxation. Various constituents in the pathways that mediate muscle contraction could act to cross-regulate cAMP or cGMP levels and terminate subsequent relaxation. We have previously shown that cAMP levels are regulated by PKA-mediated phosphorylation of cAMP-specific phosphodiesterase 3A (PDE3A) and PDE4D5; the latter is t...