Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.1.4.1 (phosphodiesterase)
18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Platelet aggregation and cyclic nucleotide (cNCL) phosphodiesterase (PDE) have been studied in a new strain of insulin-dependent spontaneously diabetic rat (SDR). The rate of aggregation of washed platelets induced by ADP or ionophore A23187 was decreased in SDR as compared to asymptomatic littermates. The activity of soluble cGMP-PDE was increased in SDR, while no significant difference was observed between SDR and control in soluble and particulate cAMP-PDE activities nor in particulates cGMP-PDE activity. Furthermore, a kinetic study of soluble cGMP-PDE in platelets demonstrated that the apparent Km was lower while the Vmax was higher in SDR. Increases were also observed in the activities of particulate cAMP-PDE and cGMP-PDE at low and high substrate concentrations in liver and heart of SDR. These anomalies of platelet aggregation and cNCL-PDE in SDR were partially correctable by insulin. For comparison, a similar study was performed in streptozotocin-induced diabetic rats (STZ). In contrast to SDR, the rate of platelet aggregation induced by ADP was increased in STZ, and the activity of soluble cGMP-PDE in platelets was decreased in STZ. A similar decrease in the activities of cAMP-PDE in liver was also observed in STZ. This study confirms observations concerning the decrease of cGMP-PDE in tissues of STZ diabetic rats. However, since opposite anomalies in PDE activity as well as a platelet function were observed in another model of diabetes (SDR), the significance of these anomalies in the pathophysiology of diabetes requires further investigation.
...
PMID:Cyclic nucleotide phosphodiesterase and aggregation in platelets from diabetic rats. 628 6

In MTP preparations from brain and EAT (isolation by the method of Doenges et al. 1977) assembled in vitro by two cycles of polymerization and depolymerization, differences appeared in the activation of the cAMP-phosphodiesterase by Ca2+ and Calmodulin. cAMP-PDE-activity in the MTP from brain is not influenced by Ca2+ or Calmodulin. However the PDE-activity in the EAT-MTP is decreased by Ca2+ (!) and is increased by Calmodulin. cGMP-PDE-activity is present in brain-MTP, and in contrast to this it is absent in MTP from EAT.
...
PMID:[Differences in the Ca2+- and calmodulin-sensitivity of cyclic nucleotide phosphodiesterase [PDE] in microtubule preparations from brain and Ehrlich-ascites-tumor cells [EAT]]. 630 28

Kidney function is regulated by several hormones which act through adenylate cyclase-cyclic AMP system. The present study was undertaken to investigate cyclic AMP- and cyclic GMP-phosphodiesterase (cAMP-PDE and cGMP-PDE respectively) activities in the rat kidney, and also the effect of several hormones affecting the kidney function on these enzyme activities in vitro. Rat kidneys were separated into cortex and medulla. These were homogenized in 50 mM Tris-HCl buffer, pH 7.5, containing 0.32 M sucrose and fractionated by centrifugation. PDE activity was measured in all fractions, using the two-step assay system. A low substrate concentration (0.5 microM) was used, unless otherwise stated. Substantial activity was present in all of the fractions and most of the activity existed in the soluble fraction (105000 X g supernatant). Cyclic GMP-PDE activity was dominant in both cortex and medulla. The rat kidney contained two forms of cAMP-PDE, one of which had a Km of 2.0 X 10(-4) M and another which had a low Km of 2.5 X 10(-5) M, and one form of cGMP-PDE with a Km of 2.5 X 10(-5) M. These cAMP-PDE and cGMP-PDE were purified by Sepharose-6B column chromatography. Cyclic AMP-PDE activity was found in a broad area associated with two peaks and cGMP-PDE activity had one peak corresponding to the same peak as the high molecular weight cAMP-PDE. Calmodulin was eluted after the peak of cGMP-PDE activity. Both cAMP-PDE and cGMP-PDE activities were inhibited by calcium ion at a concentration of more than 5.0 X 10(-4) M. Cyclic GMP-PDE activity was not activated by calmodulin in the presence of enough calcium ion. The effect of 1 alpha, 25(OH)2 Vit D3, parathyroid hormone (PTH), antidiuretic hormone (ADH), calcitonin (CT), angiotensin II, and trichlormethiazide on the partially purified cAMP-PDE and cGMP-PDE activities were examined. 1 alpha, 25(OH)2 Vit D3 activated cAMP-PDE activity and did not affect cGMP-PDE activity. The concentrations of 1 alpha, 25(OH)2 Vit D3 producing 50% activation of cAMP-PDE activity were 5.0 X 10(-11) M (cortex) and 6.7 X 10(-10) M (medulla). CT and ADH inhibited both cAMP-PDE activities. The concentrations of CT producing 50% inhibition of cAMP-PDE activity were 4.0 X 10(-5) M (cortex) and 3.3 X 10(-7) M (medulla), and those of cGMP-PDE activity were 1.0 X 10(-5) M (cortex) and 1.0 X 10(-4) M (medulla). Concerning ADH, the concentrations required for 50% inhibition of cAMP-PDE activity were 5.3 X 10(-6) M (cortex) and about 1.0 X 10(-3) M (medulla), and those of cGMP-PDE activity were 5.3 X 10(-3) M (cortex) and 5.3 X 10(-8) M (medulla).(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:[Effect of several hormones on cyclic 3',5'-nucleotide phosphodiesterase in rat kidneys]. 631 6

n-3 and n-6 polyunsaturated fatty acids are involved in the regulation of the immune response. Although different hypotheses related to modifications of arachidonic acid metabolism or alterations at the level of the cell membrane have been put forward to explain their suppressive effect on the lymphocyte growth, their mechanism of action remains largely unknown. Cyclic nucleotide phosphodiesterase (PDE) has been shown to be an important target involved in the control of lymphocyte proliferation. The present study aimed to determine whether in vitro addition of a physiological concentration (5 microM) of n-6 (20:3n-6) or n-3 (18:4n-3, 20:5n-3, 22:6n-3) fatty acids to human peripheral blood mononuclear cells (PBMC) was able to alter the PDE activity of these cells, and especially the PDE increase in response to Con A stimulation. Pretreatment of human PBMC for a short period of time (90 min) with 5 microM of either 20:3n-6, 20:5n-3 or 22:6n-3 was sufficient to induce a significant enrichment of cellular phospholipids in the corresponding fatty acid, whereas 18:4n-3 was poorly incorporated. Either fatty acid significantly increased both cAMP- and cGMP-PDE activities in the cytosolic compartment, the particulate PDE activities being less sensitive to their stimulatory effect. In contrast, they significantly lowered the PDE increase to Con A stimulation. Except 20:5 n-3, the three other fatty acids did not alter significantly the basal or Con A-induced oxygenated metabolism of arachidonic acid (AA), appreciated by the measurement of radioactive eicosanoids formed in [3H]AA-labelled cells. Furthermore, only 20:5n-3 significantly inhibited the lymphoproliferative response to Con A, whereas 16:0, 18:0, 18:1n-9, 20:3n-6 and 20:4n-6 were inactive. The inhibitory effect was not prevented by antioxidant vitamins C and E. The present results suggest that the lymphocyte growth suppressive effect of 20:5n-3 20:5n-3 is very likely to be independent on both the cAMP system and eicosanoid synthesis, and does not seem to involve their conversion to peroxidised products.
...
PMID:Influence of polyunsaturated fatty acids on lipid metabolism in human blood mononuclear cells and early biochemical events associated with lymphocyte activation. 772 18

Endothelin 3 (ET3) infusion increases the concentration of atrial natriuretic peptide (ANP) in plasma, which in turn raises hematocrit (Hct) through a transcapillary shift of plasma fluid and proteins into the interstitium, thereby reducing plasma volume (PV). The level of ANP bioactivity in peripheral target tissues is a function of ANP secretory rate and the turnover rate of ANP and its intracellular effector mechanisms. Neutral endopeptidase (NEP) is a widely distributed enzyme that participates in ANP catabolism, whereas cGMP-phosphodiesterase (PDE) degrades the intracellular second messenger of ANP. Therefore, we examined the consequences of inhibition of NEP and PDE on the ANP-dependent activity described above using the NEP inhibitor SQ 28,603 and the cGMP-PDE inhibitor zaprinast (M&B 22,948). In anesthetized, bilaterally nephrectomized rats, infusion of SQ 28,603 alone reduced mean arterial pressure (MAP) by 2.5 +/- 0.5% and increased Hct by 4.6 +/- 0.3% (P < .01 for both), leading to a calculated decrease in PV of 7.5 +/- 0.6%. These changes were prevented by pretreatment with rabbit anti-rat ANP antiserum. Simultaneous infusion of ET3 (25 ng/kg/min) and SQ 28,603 caused MAP to increase by 12.8 +/- 2.2%, an effect identical with that observed after ET3 alone (12.7 +/- 2.3%), whereas the increase in Hct of 9.4 +/- 0.4% was greater (P < .05) than the 7.5 +/- 0.4% increase seen with ET3 alone. ET3 increased plasma ANP concentration (599 +/- 135 vs. 108 +/- 13 pg/ml in vehicle-infused rats; P < .0001); ET3 and SQ 28,603 infused simultaneously increased plasma ANP even further (810 +/- 166 pg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Modulation of ANP-dependent effects of endothelin by inhibitors of neutral endopeptidase and cGMP phosphodiesterase. 775 77

Long-term scotopic (rod-mediated) visual deficits following developmental lead exposure occur in monkeys and hooded rats. This report describes and summarizes previous ERG and biochemical findings, presents new biochemical data aimed at determining the mechanism of inhibition of lead on rod cGMP-PDE, presents an integratory framework for understanding the ERG and cGMP results and speculates on the implications of the present data. A- and b-wave voltage-log intensity and latency-log intensity functions, generated from single-flash ERGs in fully dark-adapted rats, revealed that low and moderate level lead exposure caused decreases in absolute sensitivity and amplitude, and increases in latency. Rod- and cone-mediated flicker fusion frequency measures revealed selective rod deficits in temporal resolution. In addition, the slope of the increment threshold function was decreased, but only at scotopic adapting backgrounds, and dark adaptation was delayed. Prior exposure to lead produced a dose-response inhibition of retinal cGMP-phosphodiesterase (PDE) resulting in an increase in cGMP in dark-adapted and light-adapted states and an increase in the calcium content of rods. In vitro experiments with adult rat retinas incubated with 10(-9) to 10(-4) M Pb2+ revealed a concentration-dependent inhibition of cGMP-PDE which suggested that Pb2+ directly inhibited the rod cGMP-PDE. This was confirmed in experiments conducted with isolated, purified, trypsin-activated bovine rod cGMP-specific PDE exposed to 5 x 10(-8) to 10(-4) M Pb2+. The cGMP data are entirely consistent with the observed ERG changes. The ERG data is relevant to low level pediatric lead poisoning since rat rods are similar to human rods. Finally, since a lesion in the gene that codes for a cAMP-PDE leads to defective learning and memory in the Drosophila dunce flies, it is possible that lead-induced alterations in cyclic nucleotide phosphodiesterases contribute to the long-term CNS deficits produced by developmental lead exposure.
...
PMID:Lead-induced alterations in rod-mediated visual functions and cGMP metabolism: new insights. 785 84

We have investigated by immunofluorescence the appearance of immunoreactive guanosine 3'-5' cyclic monophosphate phosphodiesterase (cGMP-PDE) during the postnatal development of the retina of the pigmented rat. We show that a sudden increase in immunoreactivity takes place during postnatal day five (P5), when rod outer segments begin to form; immunoreactivity develops rapidly in the following days. Labeling is restricted to the developing photoreceptor outer segments, sparing other retinal cells, as confirmed by electron microscopy immunocytochemistry. In addition, cGMP-PDE immunoreactivity follows a center-to-periphery gradient paralleling photoreceptor differentiation. It appears that cGMP-PDE is expressed when the photoreceptor subcellular compartments are already formed, and represents a specific marker of late photoreceptor differentiation. The appearance of cGMP-PDE during development is temporally correlated with the appearance of other proteins of the phototransduction machinery.
...
PMID:Appearance of cGMP-phosphodiesterase immunoreactivity parallels the morphological differentiation of photoreceptor outer segments in the rat retina. 838 44

The bovine alpha and murine beta subunits of rod-photoreceptor cGMP-phosphodiesterase (PDE alpha and PDE beta) were expressed in adenovirus-transformed 293 human embryonic kidney cells. RNA blots from transfected cells showed transcripts of 3.0 and 2.8 kb corresponding to PDE alpha and PDE beta, respectively. Protein expression was analyzed by using affinity-purified antibodies against cGMP-PDE on immunoblots and by immunoprecipitation. PDE alpha and PDE beta exhibited the expected mobility (and thus apparent molecular size) and had cGMP hydrolytic activity. Reconstitution of the PDE alpha beta heterodimer with the expressed proteins increased by approximately 6-fold the activity of the individual alpha and beta subunits. Addition of expressed beta subunit to retinal extracts from 9- to 10-day-old rd/rd mice (which have only normal alpha and gamma subunits of rod cGMP-PDE and thus minimal activity) increased enzyme activity by approximately 3-fold. Our results therefore demonstrate that photoreceptor-specific cGMP-PDE can be synthesized in human kidney cells with consequent expression of enzymatic activity.
...
PMID:Rod photoreceptor cGMP-phosphodiesterase: analysis of alpha and beta subunits expressed in human kidney cells. 841 3

While it is known that nitric oxide (NO) is an important modulator of tone in the hypertensive pulmonary circulation, the roles of cyclic 3'-5'-guanosine monophosphate (cGMP) and cGMP-phosphodiesterase (PDE) are uncertain. We found that isolated lung perfusate levels of cGMP were over ninefold elevated in hypertensive vs. normotensive control rats. 98-100% of lung cGMP hydrolytic activity was cGMP-specific PDE5, with no significant decrease in PDE activity in hypertensive lungs, suggesting that the elevation in cGMP was due to accelerated production rather than reduced degradation. In pulmonary hypertensive rat lungs, in vitro, cGMP-PDE inhibition by E4021[1-(6-chloro-4-(3,4-methylbenzyl) amino-quinazolin-2-yl)piperdine-4-carboxylate], increased perfusate cGMP threefold, reduced hypoxic vasoconstriction by 58 +/- 2%, and reduced baseline pulmonary artery pressure by 37 +/- 5%. In conscious, pulmonary hypertensive rats, intravenous administration of E4021 reduced hypoxic vasoconstriction by 68 +/- 8%, pulmonary artery pressure by 12.6 +/- 3.7% and total pulmonary resistance by 13.1 +/- 6.4%, with no significant effect on cardiac output, systemic pressure, and resistance. Comparison of E4021 to inhaled nitric oxide demonstrated that cGMP-PDE inhibition was as selective and as effective as inhaled NO.
...
PMID:Inhibition of cyclic 3'-5'-guanosine monophosphate-specific phosphodiesterase selectively vasodilates the pulmonary circulation in chronically hypoxic rats. 855 Aug 30

The authors have previously resolved four forms of cyclic nucleotide phosphodiesterase (PDE) in neonatal rat cultured cardiomyocytes by use of high-performance liquid chromatography (HPLC) and have shown that the response of the cGMP-stimulated PDE to the effector cGMP was markedly reduced as compared to that of the corresponding isoform present in the heart ventricle of adult rat (70% v 350%). When neonatal rat ventricular myocytes were grown in a medium enriched in docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA), an increase of the basal level of cAMP and mainly cGMP was observed. The cGMP-PDE specific activity in the unfractionated cytosol of DHA-, EPA- or 8-bromo-cGMP-enriched cardiomyocytes was lower than that observed in control cells. Whereas the cAMP-PDE specific activity remained unchanged whatever the treatment used. At the same time, the response of the cGMP-stimulated PDE to cGMP was substantially increased in n-3 fatty acid-enriched cardiomyocytes and reached the same level as in the whole ventricle (340%). The treatment of neonatal cardiomyocytes with 8-bromo-cGMP also re-established the sensitivity of this cGMP-stimulated isozyme to cGMP (320%). These results suggest a common mechanism for polyunsaturated fatty acids and 8-bromo-cGMP in the regulation of the cGMP-stimulated PDE activity in cardiomyocytes from new-born rats.
...
PMID:Specific effects of n-3 fatty acids and 8-bromo-cGMP on the cyclic nucleotide phosphodiesterase activity in neonatal rat cardiac myocytes. 893 Aug 10


<< Previous 1 2 3 4 5 6 7 8 9 Next >>

---