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PDE Activity (pde + activity)

Distribution by Scientific Domains

Medical Sciences	75%

Selected Abstracts

Cyclic guanosine monophosphate phosphodiesterase activity in human gingival carcinoma

JOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 4 2003
Giuseppe Spoto
Abstract Background:, Cyclic guanosine monophosphate (cGMP) is an essential second messenger metabolized by phosphodiesterases (PDEs). Objectives:, We looked for a possible correlation of PDE activities in human oral squamous cell carcinoma (OSCC) with and without lymph node metastases. Materials and methods:, The analysis of phosphodiesterase activity and the cGMP assay were done by reverse-phase HPLC on samples of fresh or frozen gingival tissues. Analysis of cGMP was confirmed with the enzyme-linked immunoabsorption assay. Results and conclusions:, cGMP PDE activity was 34.92 ± 7.17 SD, 12.89 ± 4.43 SD, and 35.88 ± 8.76 SD (nmols/mg of protein), respectively, in controls, samples without lymph node involvement (N,), and specimens with lymph node metastases (N+). cGMP values were 1.97 ± 0.63 SD, 3.30 ± 1.47 SD, and 3.49 ± 1.47 SD (nmols/mg of protein). Our data support the hypothesis of a role for cGMP and PDE in the progression of OSCC. [source]

Regulation of intracellular cyclic GMP levels in olfactory sensory neurons

JOURNAL OF NEUROCHEMISTRY, Issue 1 2005
Cheil Moon
Abstract Cyclic AMP is the primary second messenger mediating odorant signal transduction in mammals. A number of studies indicate that cyclic GMP is also involved in a variety of other olfactory signal transduction processes, including adaptation, neuronal development, and long-term cellular responses in the setting of odorant stimulation. However, the mechanisms that control the production and degradation of cGMP in olfactory sensory neurons (OSNs) remain unclear. Here, we investigate these mechanisms using primary cultures of OSNs. We demonstrate that odorants increase cGMP levels in intact OSNs in vitro. Different from the rapid and transient cAMP responses to odorants, the cGMP elevation is both delayed and sustained. Inhibition of soluble guanylyl cyclase and heme oxygenase blocks these odorant-induced cGMP increases, whereas inhibition of cGMP PDEs (phosphodiesterases) increases this response. cGMP PDE activity is increased by odorant stimulation, and is sensitive to both ambient calcium and cAMP concentrations. Calcium stimulates cGMP PDE activity, whereas cAMP and protein kinase A appears to inhibit it. These data demonstrate a mechanism by which odorant stimulation may regulate cGMP levels through the modulation of cAMP and calcium level in OSNs. Such interactions between odorants and second messenger systems may be important to the integration of immediate and long-term responses in the setting odorant stimulation. [source]

Cyclic guanosine monophosphate phosphodiesterase activity in human gingival carcinoma

Short-term or long-term treatments with a phosphodiesterase-4 (PDE4) inhibitor result in opposing agonist-induced Ca2+ responses in endothelial cells

BRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2008
M Campos-Toimil
Background and purpose: We previously reported that agonist-induced rises in cytoplasmic Ca2+ concentration ([Ca2+]i) in human umbilical vein endothelial cells (HUVEC) were inhibited after a short-term (2 min) pre-treatment with cAMP-elevating agents. The aim of this work was to study the effects of longer term (8 h) pre-treatment with dibutyryl-cAMP (db-cAMP) or rolipram, a specific inhibitor of phosphodiesterase-4 (PDE4), on [Ca2+]i, cAMP levels and PDE activity and expression in HUVEC. Experimental approach: [Ca2+]i changes were measured in isolated HUVEC by Fura-2 imaging. Intracellular cAMP levels and PDE4 activity were assessed by enzyme-immunoassay and radio-enzymatic assay, respectively. PDE expression was measured by northern and western blot analysis. Key results: Long-term pre-treatment of HUVEC with rolipram or db-cAMP significantly increased ATP-, histamine- and thrombin-induced [Ca2+]i rises. Short-term pre-treatment with rolipram was associated with an increase in cAMP, whereas long-term pre-treatment was associated with a decrease in cAMP. Long-term pre-treatment with rolipram or db-cAMP induced a significant increase in PDE4 activity and the expression of 74 kDa-PDE4A and 73 kDa-PDE4B was specifically enhanced. All these effects were suppressed by cycloheximide. Conclusions and implications: Our data suggest that sustained inhibition of PDE4 by rolipram induced an increase in PDE4 activity, possibly as a compensatory mechanism to accelerate cAMP degradation and that PDE4A and PDE4B were implicated in the regulation of [Ca2+]i. Thus, isozyme-specific PDE4 inhibitors might be useful as therapeutic agents in diseases where [Ca2+]i handling is altered, such as atherosclerosis, hypertension and tolerance to ,-adrenoceptor agonists. [source]