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

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

As it was shown previoulsy by others, the membrane-bound phosphodiesterase (cyclic adenosine 3':5'-monophosphate phosphodiesterase) of rat epididymal fat cells was stimulated when intact cells were exposed to insulin. The levels of stimulation observed in the present study in the cell homogenate and microsomal fraction were approximately 2.0- to 2.5-fold and 2.5- to 3.0-fold, respectively, when the initial substrate level was 100 nM and insulin concentration was 1 to 3 nM. When the microsomal fraction was subjected to a sucrose density gradient centrifugation, most of the insulin-sensitive phosphodiesterase activity was fractionated into the "light" microsomal fraction which was rich in NADH2:potassium ferricyanide:oxidoreductase) and low in 5'-AMPase, adenylate cyclase, and insulin-binding activities. The latter three activities were mostly fractionated into the "heavy" microsomal fraction. Both basal and insulin-stimulated phosphodiesterase activities were low when cells were homogenized in the presence of N-ethylmaleimide or p-chloromercuribenzoate. The insulin-stimulated enzyme activity was also low when cells were homogenized in the presence of --SH compounds (e.g. dithiothreitol) or certain metal-chelating agents (e.g. ethylene glycol bis(beta-aminoethyl ehter)-N,N'-tetraacetate (EGTA)), or in a nitrogen atmosphere. The effect of EGTA was prevented by the addition of certain heavy metal ions but not by the addition of Ca2+ or Ca2+ plus Mg2+ ions. When cells were homogenized in the presence of certain oxidants (e.g. diamide, sodium tetrathionate, or air), a high plus-insulin activity was observed; this activity was not lowered by subsequent treatment of the enzyme with N-ethylmaleimede, EGTA, or fresh cell homogenate that was prepared in the presence of EGTA. However, the activity of an apparently oxidized enzyme could still be lowered by treatment woth dithiothreitol. A partially purified enzyme in the enzyme in the microsomal fraction was fairly stable both in basal and insulin-stimulated states (fully active after 35 days when kept at -20degrees). EGTA added to the homogenization buffer lowered the basal phosphodiesterase activity, but this effect was reversed by the addition of Ca2+ ions. EGTA also decreased the enzyme activity that was stimulated by norepinephrine. However, neither EGTA nor dithiothreitol had any effect on the activities of 5'-AMPase, NADH-dehydrogenase, and malate dehydrogenase of fat cells. The above data indicate that most of the insulin-sensitive phosphodiesterase and the so-called "cell membrane markers" are associated with different subcellular particles in the cell homogenate. In addition, the data seem to indicate that the insulin-stimulated phosphodiesterase has certain --SH groups and that the activity of the enzyme is stabilized when the --SH groups are oxidized by certain oxidants including molecular oxygen. It is suggested that the air oxidation of the enzyme is catalyzed by a trace of certain heavy metal ions and, therefore, can be blocked by a metal-chelating agent.
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PMID:Insulin-sensitive phosphodiesterase. Its localization, hormonal stimulation, and oxidative stabilization. 17 Feb 71

Testicular and cauda epididymal sperm were obtained via catheters previously implanted in the rete testis and proximal vas deferens of bulls and were used to examine the relationships among sperm motility, cyclic adenosine 3':5'-monophosphate (cAMP) level, adenine nucleotide levels, and rates of glucose and oxygen consumption. Testicular, cauda epididymal, and ejaculated sperm contain cAMP-stimulated protein kinase, adenylate cyclase, and nucleotide phosphodiesterase. Treatment of the nonmotile testicular sperm with phosphodiesterase inhibitors resulted in a doubling of cellular cAMP concentration and a 25% increase in their glucose consumption. No change in motility, ATP level, or rate of oxygen consumption was observed. Sperm in neat cauda epididymal semen had flagellating tails but no progressive motility. Dilution of these sperm into glucose-containing buffer resulted in an increase in intracellular cAMP concentration and a decrease in ATP level with concomitant increases in ADP and AMP levels. These biochemical changes occurred within 30 s after dilution and apparently preceded the initiation of progressive motility by most cells. Since sperm in neat cauda epididymal semen became progressively motile when diluted with neat cauda epididymal plasma as well as accessory sex gland fluid or buffer, composition of the fluid surrounding the sperm is not responsible for the initiation of progressive motility upon dilution nor does cauda epididymal plasma contain an inhibitory factor. Perhaps release from contact immobilization provides the stimulation for the initial acquisition of progressive motility by cauda epididymal sperm. We conclude that during epididymal passage sperm develop from a cell physically unresponsive to changes in cAMP concentration to a form which initiates progressive motility upon changes in cAMP concentration.
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PMID:Adenine nucleotide changes at initiation of bull sperm motility. 17 61

Interaction of adenosine-3',5'-cyclosulphate (cAMS) cAMP analogue, having sulphur atom instead of phosphorus in a six-term cyclic system with pig brain proteinkinase and rabbit skeletal muscle phosphodiesterase is studied. The affinity of proteinkinase to cAMS was found to be in 25000 times lower than the affinity of cAMP, the affinity of cAMS to the active site of phosphodiesterase being high enough. It is suggested that in the regulatory subunit of proteinkinase positive kationic group participates in nucleotide binding by interacting with negative oxygen atom of six-term cyclophosphate system. There is no such a group in the active site of phospodiesterase, because the absence of negative charge in case of cAMS only slightly affects the constant of cAMS binding by phosphodiesterase.
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PMID:[Interaction of adenosin-3',5'-cyclosulfate with adenosine-3'5'-cyclophosphate dependent protein kinase and phosphodiesterase]. 17 15

The response to combinations of gastric acid secretagogues was studied in isolated glands from the rabbit gastric mucosa in terms of changes in oxygen consumption and accumulation of the weak base aminopyrine (AP). The latter reflects the acid secreting status of the glands. The following secretagogues were investigated: histamine, carbachol, aminophylline and db-cAMP. The histamine respiratory dose-response curve was shifted to the left in the presence of the phosphodiesterase inhibitor aminophylline. Both ED-50 and maximum response were significantly increased. Histamine-induced AP accumulation was also strongly enhanced by aminophylline (5 X 10(-4) M). These results are consistent with the hypothesis that histamine stimulation of acid secretion is mediated by cyclic AMP. Carbachol-stimulated oxygen consumption could not be potentiated by aminophylline and the combined effect was only additive. The response to a combination of histamine and carbachol was a significant increase in oxygen consumption above what could be expected from an additive effect alone. Carbachol addition to glands prestimulated with histamine gave a rapid increase in the respiratory rate resulting in a new steady state level within 10-15 min, as compared with a time constant of about 40 min when both drugs were added simultaneously. Likewise AP accumulation increased more rapidly and reached a higher value after addition of histamine + carbachol as compared with histamine alone. The db-cAMP-stimulated oxygen consumption was in all respects equally affected by carbachol as was histamine stimulation. This indicates that the well known cholinergic potentiation of histamine stimulation is not due to an increased sensitivity of the histamine receptor but is of a more general nature. A mechanism involving intracellular availability of Ca2+ is proposed as one possible explanation of this potentiation.
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PMID:Potentiation by carbachol and aminophylline of histamine- and db-cAMP-induced parietal cell activity in isolated gastric glands. 19 Aug 65

Utilization of 14C-prelabeled endogenous triglycerides was studied in isolated perfused working rat hearts. Lipolysis was estimated by the disappearance of 14C-labeled and total triglycerides. Metabolic 14CO2 production was continuously monitored to evaluate triglyceride fatty acid oxidation. Triglyceride utilization was enhanced by an increase in ventricular pressure development as evidenced by a faster rate of triglyceride mobilization and oxidation. Added catecholamines stimulated lipolysis in hearts perfused with glucose-containing buffer but were without effect in the presence of exogenous fatty acids; the latter were shown to be potent and, possibly, direct inhibitors of myocardial lipolysis. Mediation of catecholamine-induced lipolysis by cyclic AMP has not been settled. Dibutyryl cyclic AMP produced only a slight lipolytic effect, although theophylline, a known phosphodiesterase inhibitor, was a potent lipolytic agent. Theophylline may have exerted its lipolytic effect through an alternative mechanism. Hypoxia per se was a strong inhibitor of heart triglyceride utilization. Furthermore, added epinephrine was without effect on triglyceride lipolysis in hypoxic hearts. Thus, cardiac muscle triglyceride utilization is influenced by such factors as mechanical function, exogenous substrates, hormones, and oxygen availability. The mechanisms involved in these areas of regulation need to be resolved.
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PMID:Regulation of triglyceride metabolism in the isotopically prelabeled perfused heart. 19 38

It is known that dibutyryl cyclic AMP (dbcAMP) and theophylline inhibit the spontaneous maturation of isolated mouse oocytes. The present study demonstrates that dbcAMP (0.01-1.0 mM) as well as cyclic AMP (cAMP, 10 mM) and a phosphodiesterase inhibitor (IBMX, 0.01-1.0 mM) prevent spontaneous maturation of isolated rat oocytes. As reported earlier an increase in oxygen consumption by the oocyte was found following maturation. When the oocytes were cultured in the presence of dbcAMP or cAMP no change in respiration occurred during culture. These results argue against the theory that cAMP acts as a direct mediator of the action of luteinizing hormone (LH) on oocyte maturation. Furthermore they suggest that changes in oocyte energy metabolism are closely related to the maturation process.
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PMID:Inhibition of maturation and metabolism in rat oocytes by cyclic amp. 19 33

Islets microdissected from ob/ob-mice were exposed to 3mM pentobarbital in media which were normal or deficient in Ca2+. This treatment resulted in marked decrease of the islet content of cyclic AMP recorded in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. Pentobarbital had a dual effect on insulin release. In addition to being a potent inhibitor of glucose-stimulated insulin release in media containing 2.56 mM Ca2+ it increased the amounts of insulin released in high glucose media deficient in Ca2+. There was a transient stimulation with ordinary concentrations of Ca2+ and 3mM glucose whtn the media also contained 3-isobutyl-1-methylxanthine. The stimulatory effect of pentobarbital persisted after replacing part of the Ca2+ in the beta-cell membrane with lanthanum ions and it could not be mimicked by lowering the oxygen tension of the incubation medium. It is suggested that pentobarbital stimulation of insulin release is the result of a specific action of the drug on the distribution of Ca2+ within the pancreatic beta-cells.
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PMID:Calcium and pancreatic beta-cell function. I. Stimulatory effects of pentobarbital on insulin release. 19 66

Aqueous solutions of DNA were gamma-irradiated in the presence and absence of oxygen and enzymatically hydrolysed by the combined action of pancreatic deoxyribonuclease (DNase I), snake-venom phosphodiesterase (PDE I), spleen phosphodiesterase (PDE II) and alkaline phosphatase. In contrast to unirradiated DNA, which is fully hydrolysed to nucleosides by these enzymes, gamma-irradiated DNA yields a series of oligonucleotides. Their isolation might enalbe the future identification of the chemical nature of DNA lesions.
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PMID:Enzymatic digestion of DNA gamma-irradiated in aqueous solution separation of the digests by ion-exchange chromatography. 21 Jan 33

Ethyl carbamate, labelled at C1 with 14C, bound in vivo to liver DNA of intact and partially hepatectomised mice. Isotope (18O) enrichment was not detected in the oxygen of liver DNA of mice injected with [18O] ethyl carbamate, C2H5--18O--CO--NH2. This suggests that it was the ethyl group and not the ethoxy group which bound to DNA. Chromatographic analysis of acid hydrolysates of liver DNA from mice treated with [1-14C] ethyl carbamate provided no evidence of alkylation or other form of binding to purine or pyrimidine bases. On relatively mild acid hydrolysis the alkyl group remained bound to the "apurinic acid" fraction, while more vigorous hydrolysis lead progressively first to its separation as highly ionisable hydrophilic non-volatile compounds and then to its loss as a volatile compound. DNAase I followed by phosphodiesterase hydrolysis also split off the 14C-containing group as a volatile compound. The volatile compound was identified as ethanol. These results suggest that the alkyl group was bound as an ester to a phosphate group in the DNA chain. Results with DNA from partially hepatectomised mice did not differ from those with DNA from intact mice.
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PMID:The binding of ethyl carbamate to DNA of mouse liver in vivo: the nature of the bound molecule and the site of binding. 95 35

Trapidil increases the isoprenalin-induced necrosis of the myocardium in the rat. In the paper is referred to the importance of the term of application in relation to the application of the infarcting noxa. Trapidil has a particularly unfavourable effect, if it is given after isoprenalin. The shift of the relation from the oxygen requirement to the oxygen supply by beta-adrenergic stimulation is regarded as an equivalent for the acute ischaemia. The authors see a connection between the phosphodiesterase-inhibiting activity of trapidil and the influence of the size of necrosis after the application of isoprenalin in the rat. These findings have also clinical importance, as the area of indication explicitly includes the application after fresh myocardial infarction and in acute pectanginous attack.
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PMID:[Modification of the isoprenaline-induced myocardial necrosis using trapidil]. 100 38


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