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)

Administration of hydrocortisone into healthy rabbits activated adenilate cyclase and phosphodiesterase in liver tissue; activity of the enzymes was normalized within 5 days after the treatment. The hormone, administered into animals with experimental cholesterol-induced atherosclerosis, caused an activation of adenilate cyclase and inhibition of phosphodiesterase; due to the phenomenon more distinct and long-term increase in cAMP concentration was observed in kidney, liver and fatty tissues. Concentration of cAMP exceeded considerably its initial content in the tissues within 5 days after the hydrocortisone administration. Hydrocortisone inhibited the adenilate cyclase system activity in adrenal cortex of experimental and control animals at early period of the experiment. In health rabbits content of cAMP was increased in adrenal cortex within 5 days after the hormone administration. As the similar effect was not found in animals with experimental atherosclerosis these data suggest that the hypophysis-adrenal cortex system under the experimental conditions studied was inhibited.
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PMID:[Effect of cortisol on adenylate cyclase and 3',5'-AMP phosphodiesterase activity and 3',5'-AMP concentration in tissues and biological fluids in experimental atherosclerosis]. 20 90

Hypercholesterolemia caused a decrease in the activity of adenylcyclase in rabbit liver tissue and in thrombocytes; hypertriglyceridemia, which developed after administration of hydrocortisone, led to an increase in the activity of adenylcyclase and in the content of 3,5-AMP in adipose tissue. Activities of adenylcyclase, phosphodiesterase and content of prostaglandines E1 and F2alpha were measured in thrombocytes of 39 healthy men without any symptoms of of ischemic heart impairment, in 52 patients with coronary atherosclerosis of the III degree (by Myasnikov's classification) as well as in 12 patients during the period of rehabilitation after myocardial infarction. The activity of adenylate cyclase system was impaired in atherosclerosis. This phenomenon might be caused by alteration in concentration of glucocorticoids in the organism.
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PMID:[Cyclic adenosine monophosphate and atherogenic factors]. 20 91

Hypercholesterolemia and hypertension are two of the major risk factors associated with increased atherosclerotic vascular disease. An abnormal platelet function is one of the mechanisms proposed to participate in atherogenesis. This study was undertaken to find out whether hypercholesterolemia in hypertensive patients can change platelet lipid composition and reactivity. Twenty-nine untreated hypertensive patients were distributed into 3 age, body mass index and blood pressure-matched groups according to their plasma cholesterol levels (normal, borderline or elevated, group NC, BC and HC respectively). Their platelet lipid composition, cytosolic Ca2+ concentration, cyclic AMP content and aggregating response to ADP and collagen were determined. Platelet from group HC patients were characterized by reduced cyclic AMP content (evaluated in the presence and absence of a platelet phosphodiesterase inhibitor) and aggregating responses to ADP and collagen, increased palmitic acid content and decreased arachidonic, eicosapentaenoic and docosatetraenoic and pentaenoic acid content, resulting in a lowered polyunsaturated to saturated fatty acid ratio (P less than 0.001). In contrast, platelet cytosolic Ca2+ concentration, DPH steady-state anisotropy and cholesterol to phospholipid molar ratio were not significantly changed. This indicates that hypercholesterolemia is accompanied in hypertensive patients by marked changes in platelet fatty acid composition, cyclic AMP content and response to aggregating agents. These changes, which clearly differ from those induced by in vitro cholesterol loading, could reflect not only the balance between LDL and HDL stimulation but also an adaptation to hemodynamic perturbations.
Atherosclerosis 1992 Jun
PMID:Biochemical and functional alterations associated with hypercholesterolemia in platelets from hypertensive patients. 132 32

Flavonoids are a vast group of natural substances, but their pharmacological properties have not all been explored. The term flavonoid is used at large to designate a series of more than 4,000 molecules, which in fact can have very heterogenous molecular structures. We have shown that some flavonoids are good inhibitors of cyclic nucleotide phosphodiesterase (PDE). The most active PDE inhibitors among the flavonoids were also good inhibitors of the aggregation of human platelets in vitro. This suggests that flavonoids could serve as a template for the development of new anti-platelet drugs. However, a direct extrapolation of our experimental results to possible therapeutical use of flavonoid-containing medicinal plant extracts is not possible. The metabolic fate of these plant flavonoids is poorly understood, and their absence of toxicity has not always been clearly demonstrated. Flavonoids are also present in a regular diet in significant amounts. The role of these dietary flavonoids in the prevention of thrombotic diseases or atherosclerosis should also be investigated.
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PMID:[Flavonoids: antithrombotic agents or nutrients?]. 227 80

We investigated the effect of hyperlipidemic serum on cAMP accumulation in cultured smooth muscle cells from the rabbit aorta. The cells were grown to confluence, then cultured for 24 h in hyperlipidemic medium (total cholesterol: 2.2 mmol/l). cAMP accumulation was enhanced in response to isoproterenol 10(-6) M, as compared to control cells, and this enhancement was still detectable in the presence of IBMX 10(-3) M, a potent inhibitor of phosphodiesterase. Application of propranolol 10(-4) M at 5 min after isoproterenol showed a similar time course for cAMP disappearance. The phosphodiesterase activity in the 40 000 g supernatant of the Triton X-100 solubilized homogenates of the cells in hyperlipidemic medium remained unchanged. Beta-receptor assays showed an increased Bmax with a similar Kd, and such may contribute, at least in part, to the increased adenylate cyclase activity. An extended incubation in the presence of hyperlipidemic medium attenuated the cAMP accumulation, possibly due to excessive increases in the total cholesterol content.
Atherosclerosis 1985 Aug
PMID:Cyclic AMP accumulation in rabbit aorta smooth muscle cells altered in the presence of hyperlipidemic serum. 241 25

A primary culture of cells derived from uninvolved and atherosclerotic intima of human aorta was used to elucidate the role of cyclic nucleotides in atherogenesis. The cells cultured from fatty streaks and atherosclerotic plaques had a 2- to 8-fold lower cyclic AMP level and a 1.5- to 2-fold higher level of cyclic GMP compared with those of a grossly normal intima. Medial cells cultured from nonlesioned and atherosclerotic aortic segments showed no differences in the cyclic nucleotide concentrations. Reduction of the intracellular cyclic AMP with 2'-deoxyadenosine or a cyclic GMP elevation with its dibutyryl derivative, or liposomes containing cyclic GMP stimulated the uptake of [3H]thymidine and protein synthesis in the cells cultured from unaffected intima. On the contrary, a rise of the intracellular cyclic AMP caused by adenylate cyclase activators, a phosphodiesterase inhibitor, dibutyryl cyclic AMP, and liposomes containing cyclic AMP inhibited cell proliferation and protein synthesis. Elevation of the intracellular cyclic AMP stimulated the hydrolysis of lipids which led to reduction of lipid levels in the cells cultured from atherosclerotic lesions. The results of this study corroborate the existence of a relationship between the alterations of intracellular cyclic nucleotide levels and the metabolic disorders occurring in atherosclerosis.
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PMID:Cyclic nucleotides and atherosclerosis: studies in primary culture of human aortic cells. 244

We performed an in vitro study to assess injury to vascular endothelial cells by platelets. Cultured endothelial cells isolated from fetal bovine aorta were used. Addition of human platelets, activated by collagen or lysed by sonication, to the culture dish resulted in dose- and time-dependent damage to the cells as estimated by [3H]adenine release. Analysis of [3H]adenine nucleotides by thin-layer chromatography on PEI-cellulose revealed decreased intracellular ATP content in the cells treated with platelet lysate. The medium contained AMP and adenosine, the latter increasing following the treatment of the cells. Of the substances released by the activated platelets, thromboxane A2 (TxA2) and serotonin caused cell damage. Platelet-derived growth factor (PDGF), however, did not damage the endothelial cells up to a concentration of 200 ng/ml. Pretreatment of the cells with methysergide (10(-6) M) or ONO 3708 (10(-5) M), a TxA2 antagonist, only partially prevented the damage, while ZK 36374 (10(-6) M), a prostacyclin analog, and 3-isobutyl-1-methylxanthine (IBMX; 10(-3) M), a phosphodiesterase inhibitor, potently inhibited injury. We conclude that the substances released from activated platelets may injure endothelial cells in an additive or synergistic manner and that agents which produce effects that elevate cyclic AMP levels may protect the cells from damage induced by the platelets.
Atherosclerosis 1989 Apr
PMID:In vitro study of vascular endothelial injury by activated platelets and its prevention. 254 23

It has been suggested that elevated levels of insulin may be related to the development of atherosclerosis in both diabetics and non diabetics. Although insulin receptors are present on the cell membranes of both arterial endothelial and smooth muscle cells, insulin has growth-promoting and metabolic activities only on smooth muscle cells. In the present study, dibutyryl cAMP at concentration 0-1.0 mM decreased insulin binding in bovine aortic smooth muscle cells but had no effect on endothelial cells. At 2.0 mM dibutyryl cAMP had no effect on either cell type. The effect of dibutyryl cAMP was paralleled by its analogue 8-Br-cAMP and by MIX, a phosphodiesterase inhibitor. To test whether LDL receptor activity is influenced by insulin in arterial smooth muscle cells, the effect of insulin on LDL binding, uptake and degradation in bovine aortic smooth muscle cells was studied. Pre-incubation for 24 h with insulin at concentration 0-100 microU/ml resulted in a doubling of LDL binding, whereas pre-incubation for 4 h had no effect. Thus the differential effect of insulin on arterial endothelial and smooth muscle cells is similar to the effect of cAMP on insulin binding in these cells. Insulin increases binding of LDL to smooth muscle cells.
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PMID:Effects of insulin and glucose on the cells of the arterial wall: interaction of insulin with dibutyryl cyclic AMP and low density lipoprotein in arterial cells. 282 Aug 12

Spontaneously hypertensive rats (SHRSP and SHR) and normotensive WKR were treated with hypotensive drugs, and arterial and venous enzyme activities were compared between treated and nontreated hypertensive groups. With the 4 month experiment, cholesterol esterase activity in the aorta from hypertensive SHRSP and SHR was significantly lower than that in the respective treated groups, whereas venous activity did not differ. By contrast, aortic NAGA activity was significantly higher in the hypertensive groups without any changes in venous activity. Acid phosphatase activity was unaltered. No effects of treatment were observed in the normotensive WKR. Accompanying a decrease in aortic cholesterol esterase, there was a marked increase in aortic cholesteryl esters accompanying hypertension. Aortic phosphodiesterase activity was significantly elevated in the hypertensive SHRSP and SHR compared with the respective treated groups. These results suggest that hypertension of long duration specifically decreased aortic cholesterol esterase activity with a consequent accumulation of cholesteryl esters in the aorta, and that this hemodynamic effect seemed to be partly mediated by cyclic AMP with an effect on the lysosomal membrane. These results could provide the biochemical bases for the relationship between hypertension and atherosclerosis.
Atherosclerosis 1980 Nov
PMID:Hemodynamic effects on aortic enzyme activities in spontaneously hypertensive rats. 625 51

Metabolism of arachidonic acid (AA) in blood platelets and in vascular endothelium does not lead to prostaglandins, but thromboxane A2 and prostacyclin are generated. These labile metabolites of AA antagonize each other: thromboxane A2 is a vasoconstrictor and proaggregatory agent, whereas prostacyclin dilates arteries, prevents platelets from aggregation, and dissipates the preformed platelet clumps. Prostacyclin is a powerful stimulator of adenylate cyclase in platelets and therefore its antiplatelet action is potentiated by phosphodiesterase inhibitors such as theophylline or dipyridamole. Cyclo-oxygenase of AA is inhibited by aspirin, thromboxane synthetase by analogues of prostaglandin endoperoxides, and prostacyclin synthetase by linear lipid peroxides. A hypothesis is put forward that atherosclerosis develops because of pathological, nonenzymic lipid peroxides. A hypothesis is put forward that atherosclerosis develops because of pathological, nonenzymic lipid peroxydation in the body and the subsequent molecular damage to prostacyclin synthetase in the rheologically determined areas of arterial walls. Endothelium deprived of prostacyclin is the basis for microthrombi formation, and follows a sequence of events described by Rokitansky and later by Ross. Prostacyclin is also a circulating hormone which is generated by the lungs. Thereby a damage of this "endocrine gland" by respiratory disorders, air pollution, or tobacco smoking are likely to contribute to pathogenesis of atherosclerosis, myocardial infarction, and arterial thromboembolism. Pharmacological treatment and prevention of these diseases should logically include antioxydants, prostacyclin and its analogues, thromboxane synthetase inhibitors and perhaps cyclooxygenase inhibitors (aspirin ?). Prostacyclin was already infused intravenously to men and its powerful antiaggregatory and deaggregatory actions were demonstrated. These properties of prostacyclin along with its vasodilator and positive inotropic actions destine this hormone to be a new type of antithrombotic drug in acute myocardial infarction.
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PMID:Prostaglandins, platelets, and atherosclerosis. 677 Nov 2


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