Elevation in cell cAMP content can inhibit mitogenic signaling in cultured human airway smooth muscle (HASM) cells. We studied the effects of the type 3-selective phosphodiesterase inhibitor siguazodan, the type 4-selective phosphodiesterase inhibitor rolipram, and the nonselective inhibitor 3-isobutyl-1-methylxanthine (IBMX) on proliferation of cultured HASM cells. At concentrations selective ...

OBJECTIVE To compare the direct pulmonary vasodilating activity and specificity of phosphodiesterase-5 (zaprinast) and phosphodiesterase-3 (milrinone) inhibitors on the pulmonary vascular (PV) bed of the spontaneously breathing cat with an intact chest. DESIGN Prospective, randomized animal study. SETTING Laboratory of university hospital. SUBJECTS Experiments were performed in vivo in in...

Abstract Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by erythema and pruritis, affecting over 15 million people in the US. Th2/Th17 cytokines play key role AD pathogenesis, resulting an increased response, disrupted barrier, susceptibility to infections allergen sensitization. Phosphodiesterase 4 (PDE4) cyclic 3’,5’-adenosine monophosphate (cAMP)-specific phospho...

OBJECTIVES Sildenafil citrate, a specific phosphodiesterase-5 inhibitor, is increasingly used for pulmonary hypertension in pregnancy. Sildenafil is also emerging as a potential candidate for the treatment of intra-uterine growth retardation and for premature labor. Its effects in the feto-placental circulation are not known. Our objectives were to determine whether phosphodiesterase-5 is prese...

Extracts of a mutant S49 lymphoma cell line, termed K30a, hydrolyze cAMP and cGMP at rates much faster than do wild type S49 extracts. This elevated phosphodiesterase activity, called K-PDE, elutes as a single peak of activity on DEAE-cellulose columns (Brothers, V. M., Walker, N., and Bourne, H. R. (1982) J. Biol. Chem. 257, 9349-9355). Direct photoaffinity labeling of K30a extracts with [32P]...

The central phosphatase domain of Clostridium thermocellum polynucleotide kinase/phosphatase (CthPnkp) belongs to the dinuclear metallophosphoesterase superfamily. Prior mutational studies of CthPnkp identified 7 individual active site side chains (Asp-187, His-189, Asp-233, Asn-263, His-323, His-376, and Asp-392) required for Ni2+-dependent hydrolysis of p-nitrophenyl phosphate. Here we find t...

Adenosine 3':5'-monophosphate (cyclic AMP) phosphodiesterase activity of normal human peripheral blood leukocyte suspensions containing 90% lymphocytes and 10% monocytes showed anomalous kinetic behavior indicative of multiple enzyme forms. Kinetic analyses of purified lymphocyte (99%) or monocyte preparations (95%) indicated that only one type of phosphodiesterase was present in each cell type...

A single specifically labeled protein (Mr = 42,000) is found when Dictyostelium discoideum crude membrane (ghost) preparations are photoaffinity-labeled with either [32P]8N3-cAMP or [32P]8N3-AMP. With the CAMP reagent, there is a close correlation between the labeling of this protein and the membrane phosphodiesterase activity. During cell differentiation the developmental time courkes of the p...

Isolated fat cells from hypothyroid rats, in contrast with those from normal animals, lack ability to give a lipolytic response to epinephrine or glucagon. However, activation of triglyceride lipolysis was induced with (N6,02’-dibutyryl cyclic adenosine 3’ :5’-monophosphate), or a combination of epinephrine and phosphodiesterase inhibitors. Adenylyl cyclase was activated by catecholamines or gl...