Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intravenous injection of chicks with bovine parathyroid hormone (1-34) (3.3 micrograms/100 g body wt.) or 16,16-dimethyl PGE2 (5 micrograms/100 g body wt.) caused rapid (3 minute) net inhibition of 45Ca uptake into femur and calvarium. These agents also elevated bone adenosine 3',5'-cyclic monophosphate (cAMP) but not guanosine 3',5'-cyclic monophosphate (cGMP) levels at this time. Methylxanthine phosphodiesterase inhibitors (MXPI), caffeine, theophylline, and 3-isobutyl-1-methylxanthine (IBMX) (0.3-5 mg/100 g body wt.) similarly inhibited net 45Ca uptake into femur and to a lesser extent calvarium. Plasma 45Ca and total Ca levels were unaltered or showed a slight tendency to be increased over control values 3 minutes after injection. However, the effects of the non-MXPI, dibutyryl-cAMP (0.5-5 mg/100 g body wt.) on bone 45Ca uptake were negligible. Of the MXPI, only IBMX elevated total cAMP levels in chick bone at 3 minutes. These data implicate but do not confirm a mediatory role for cAMP in the rapid inhibitory actions of PTH and PGEs on bone net 45Ca uptake in chicks.
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PMID:Cyclic nucleotides and the rapid inhibitions of bone 45Ca uptake in response to bovine parathyroid hormone and 16,16-dimethyl prostaglandin E2 in chicks. 246 12

The combination of coronary heart disease (CHD) with increased left ventricular wall mass (LVWM) appears associated with prolonged isovolumetric relaxation (IVR) and consequently, alterations in the rapid filling phase. Methylxanthine-substances may improve relaxation through inhibition of phosphodiesterase activity. Accordingly we examined multiple indexes of left ventricular diastolic function before and after administration of 200 mg pentoxifylline (Trental) intravenously to 18 patients (51.3 +/- 9.0 years, 15 males, three females) with stable angina pectoris and positive exercise-ECG in NYHA class I or II and LVWM greater than 160 g (n = 9) and less than or equal to 160 g (n = 9). Left ventricular pressure (P) and volume (V) measurements were made with a high-fidelity-micromanometer before and twelve minutes after administration of pentoxifylline. The time constant of left ventricular isovolumic relaxation (T), usual global left ventricular volumes and derived indexes such as peak filling rate (PFR), time to peak filling rate (TPFR), segmental (relaxation and rapid filling phases) and total pressure-volume relationship before and after pentoxifylline were calculated. Significant differences between these two groups (greater than/less than or equal to 160 g LVWM) were found for end-diastolic volume (68.7 +/- 19.0 to 90.8 +/- 22.6 ml/sqm), end-systolic volume (21.7 +/- 16.0 to 36.1 +/- 14.7 ml/sqm), end-diastolic pressure (15.0 +/- 4.8 to 15.7 +/- 5.1 mm Hg), PFR (3.25 +/- 1.18 to 2.66 +/- 0.71 s-1), T (46.0 +/- 5.7 to 52.7 +/- 7.2 ms), the linear regression of lnP-V (lny = -0.117 x + 4.59 to lny = -0.091 x + 4.75) in the IVR-phase (dp/dtmin less than or equal to x less than or equal to 80 ms) (leftward shift in p-V-relationship when less than or equal to 160 g) and the complet p-V-areas. After pentoxifyl-line-administration there were significant decreases in T in patients with increased LVWM (52.7 +/- 7.2 to 47.7 +/- 5.9 ms) and the P-V-product over the time in the rapid filling phase in patients with LVWM less than or equal to 160 g. Total peripheral resistance and heart rate did not change. These changes in parameters of left ventricular diastolic function in combination with significant improvement of pump function especially in patients with LVWM greater than 160 g after administration of pentoxifylline suggest that improved diastolic function is the result of a direct myocardial effect of pentoxifylline.
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PMID:[Effects of pentoxifylline on diastolic heart function in patients with angina pectoris and an increased left ventricular wall mass]. 296 93

Family 18 chitinases have a binding capacity with chitin, a polymer of N-acetylglucosamine. Recent studies strongly suggested that chitinase 3-like 1 (CHI3L1, also known as YKL-40) and acidic mammalian chitinase, the two major members of family 18 chitinases, play a pivotal role in the pathogenesis of inflammatory bowel disease (IBD), bronchial asthma and several other inflammatory disorders. Based on the data from high-throughput screening, it has been found that three methylxanthine derivatives, caffeine, theophylline, and pentoxifylline, have competitive inhibitory effects against a fungal family 18 chitinase by specifically interacting with conserved tryptophans in the active site of this protein. Methylxanthine derivatives are also known as adenosine receptor antagonists, phosphodiesterase inhibitors and histone deacetylase inducers. Anti-inflammatory effects of methylxanthine derivatives have been well-documented in the literature. For example, a beneficial link between coffee or caffeine consumption and type 2 diabetes as well as liver cirrhosis has been reported. Furthermore, theophylline has a long history of being used as a bronchodilator in asthma therapy, and pentoxifylline has an immuno-modulating effect for peripheral vascular disease. However, it is still largely unknown whether these methylxanthine derivative-mediated anti-inflammatory effects are associated with the inhibition of CHI3L1-induced cytoplasmic signaling cascades in epithelial cells. In this review article we will examine the above possibility and summarize the biological significance of methylxanthine derivatives in intestinal epithelial cells. We hope that this study will provide a rationale for the development of methylxanthine derivatives, in particular caffeine, -based anti-inflammatory therapeutics in the field of IBD and IBD-associated carcinogenesis.
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PMID:Novel methylxanthine derivative-mediated anti-inflammatory effects in inflammatory bowel disease. 2457 89

Intracellular cyclic AMP and/or cyclic GMP are characterized in the 1960th. These second messengers, hydrolysed specifically by cyclic nucleotide phosphodiesterase (PDE), play a major role in intracellular signalling. Natural products have been a rich source of drug discovery, Theophylline and Methylxanthine originated from tea leaves used for asthma treatment, whereas, Papaverine, a natural isoquinolein originated from Papaver somniferum traditionally used in impotency, altogether as caffeine where firstly described as PDE-inhibiting compounds. Since that time, the knowledge in PDE field has been drastically increased, allowing the design and development of new therapeutic drugs acting against different pathologies in the nanomolar range. During this period some natural compounds have been identified as PDE inhibitors and used in that context to investigate their therapeutic potential effects. The aim of this literature review is to point out the reported data and demonstrating the contribution of natural characterized molecules as PDE inhibitors in various pathologies that can open new fields of research for drug discovery, notably in epigenetic regulation.
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PMID:Therapeutic potentials of natural compounds acting on cyclic nucleotide phosphodiesterase families. 2875 27