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)

The influence of amitryptiline, theophylline and furosemide on the concentration of cyclic-AMP and plasma renin activity (PRA) was investigated in renal vein plasma. Additionally, the stimulating effect of furosemide on the PRA after application of the beta-adrenergic receptor antagonists propranolol and practolol and the cyclic AMP concentration in the plasma were measured. All drugs were given intravenously. After amitryptiline cyclic-AMP concentration increased about 1.5-fold compared with the basal value,PRA was not altered. After theophylline cyclic-AMP concentration increased about 1.2-fold, PRA 2.0-fold compared with the basal value, PRA was not altered. After theophylline cyclic-AMP concentration increased about 1.2-fold, PRA 2.0-fold coa increased within 7 min and no further increase was observed till the 15th min. After practolol cyclic-AMP concentration and PRA decreased about 20% compared with the basal value within 10 min. The stimulating effect of subsequently applied furosemide on PRA was not altered, but the cyclic-AMP concentration was not changed in this time by furosemide. After propranolol cyclic-AMP concentration and PRA decreased about 20% compared with the basal value. The cyclic-AMP concentration was not influenced by the following furosemide application, in agreement with the findings after practolol, however, PRA could be stimulated only in 36% of these patients under beta-receptor blockade. Our results show that changes of the concentrations of cyclic-AMP and of PRA are independent of each other. An elevated intracellular cyclic-AMP level due to the inhibition of phosphodiesterase is as a single factor unable to stimulate renin release. Our results give no evidence of a direct involvement of the adenylcyclase-system in the mechanism of renin release. The effect of propranolol and practolol on the basal value of PRA and cyclic-AMP is equal. The different influence of 10 mg propranolol and 20 mg practolol on the stimulating effect of 40 mg furosemide on the PRA can be interpreted as a dosage problem.
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PMID:[Cyclic AMP and plasma renin activity in renal vein blood after amitryptiline, theophylline, furosemide and beta adrenergic blocking substances (author's transl)]. 1 4

ADP-induced platelet aggregation and shape change were monitored optically in citrated rabbit platelet-rich plasma (PRP) diluted with isotonic salt solutions. Lithium (Li) produced a concentration-dependent reduction in the rate of platelet aggregation but had no discernible effect on the shape change which precedes aggregation. When PRP was pre-incubated with Li, the inhibitory effect of the ion was independent of the duration and temperature of the treatment. The inhibitory effect of Li also was observed in heparinized PRP or when 5-HT was used as the aggregation-inducing agent. When Li was combined with aggregation inhibitors which enhance platelet cyclic AMP content either by activating adenylate cyclase or by inhibiting phosphodiesterase, only additive effects were observed. The inhibitory effect of Li was opposed by added calcium. Kinetic evaluation of the interaction between Li and Ca indicated that their antagonism was competitive. Added calcium also displayed competitive antagonism toward the aggregation inhibiting effect of increased hydrogen ion concentration in the pH range between 6 and 8.
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PMID:Competitive inhibition by lithium and hydrogen ions of the effect of calcium on the aggregation of rabbit platelets. 1 92

A highly purifed preparation of rat intestinal phosphodiesterase II (oligonucleate 3'-nucleotidohydrolase, EC 3.1.4.18) has been studied using a synthetic substrate, thymidine 3'(2,4-dinitrophenyl) phosphate. The enzyme was most active between pH 6.1 and pH 6.7 and was inhibited by Cu2+ and Zn2+ but unaffected by EDTA, Mg2+, Co2+, and Ni2+. The reaction rate decreased at high levels of enzyme because of competitive inhibition by deoxythymidine 3'-phosphate, a reaction product, which showed a Ki of 2-10(-5) M. The molecular weight of the enzyme by gel-filtration was 150 000-170 000. In electrofocusing experiments multiple peaks of activity were found at pH 3.4, 4.2-4.5and 7.2. Polyacrylamide gel electrophoresis of freshly purified phosphodiesterase II showed up to 10 protein bands in the gels. If the preparations were stored at 4 degrees C for some time only one or two bands appeared. Investigation of the reaction of rat intestinal phosphodiesterase II with a number of possible phosphodiesterase substrates indicated that the enzyme required a nucleoside 3'-phosphoryl residue for the initiation of hydrolysis. Thus compounds such as NAD, ATP, bis-(p-nitrophenyl)phosphate, thymidine 5'-(p-nitrophenyl)phosphate, glycerylphosphorylcholine, guanylyl-(2' leads to 5')-adenosine and 3',5'-cyclic AMP which contain phosphodiester bonds, nevertheless were not substrates for the enzyme. The enzyme was inhibited reverisbly by p-chloromercuribenzoate and p-chloromercuriphenylsulfonate and inactivated irreversibly by iodoacetic acid. Activity of the phosphodiesterase II was reduced to 50% by incubation with 2.0-10(-3)--5.0-10(-3) M iodoacetate for 20--30 min at 24 degrees C at pH 5.0--6.1. Iodoacetamide had no effect. The degree of inactivation by iodoacetate was reduced by the presence of a substrate for the enzyme or, more effectively by deoxythymidine 3'-phosphate, a competitive inhibitor. It is concluded that iodoacetic acid alkylates an essential residue at the active centre of the enzyme.
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PMID:Rat intestinal phosphodiesterase II. Properties of the highly purified enzyme and its inactivation by iodoacetic acid. 1 24

DNA-binding protein HD with a monomer molecular weight of 9000 was isolated from Escherichia coli cells. The protein occurs as a tetramer under native conditions and binds to single and double-stranded DNA and also to RNA. DNA complexed with protein HD is a poor template for DNA synthesis by E. coli polymerase I, II or III holoenzyme. Exonuclease III is hindered in degrading HD-protein-covered double-stranded DNA, whereas exonuclease I can digest complexed single-stranded DNA. Transcription is liqhtly stimulated in the presence of protein HD.
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PMID:Interaction of DNA with DNA-binding proteins. The characterization of protein HD from Escherichia coli and its nucleic acid complexes. 1 66

Phosphodiesterase activities of horse (and dog) thyroid soluble fraction were compared with either cyclic AMP (adenosine 3':3'-monophosphate) or cyclic GMP (guanosine 3':5'-monophosphate) as substrate. Optimal activity for cyclic AMP hydrolysis was observed at pH 8, and at pH 7.6 for cyclic GMP. Increasing concentrations of ethyleneglycol bis(2-aminoethyl)-N,N'-tetraacetic acid inhibited both phosphodiesterase activities; in the presence of exogenous Ca2+, this effect was shifted to higher concentrations of the chelator. In a dialysed supernatant preparation, Ca2+ had no significant stimulatory effect, but both Mg2+ and Mn2+ increased cyclic nucleotides breakdown. Mn2+ promoted the hydrolysis of cyclic AMP more effectively than that of cyclic GMP. For both substrates, substrate velocity curves exhibited a two-slope pattern in a Hofstee plot. Cyclic GMP stimulated cyclic AMP hydrolysis, both nucleotides being at micromolar concentrations. Conversely, at no concentration had cyclic AMP any stimulatory effect on cyclic GMP hydrolysis. 1-Methyl-3-isobutylxanthine and theophylline blocked the activation by cyclic GMP of cyclic GMP of cyclic AMP hydrolysis, whereas Ro 20-1724 (4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone), a non-methylxanthine inhibitor of phosphodiesterases, did not alter this effect. In dog thyroid slices, carbamoylcholine, which promotes an accumulation of cyclic GMP, inhibits the thyrotropin-induced increase in cyclic AMP. This inhibitory effect of carbamoylcholine was blocked by theophylline and 1-methyl-3-isobutylxanthine, but not by Ro 20-1724. It is suggested that the cholinergic inhibitory effect on cyclic AMP accumulation is mediated by cyclic GMP, through a direct activation of phosphodiesterase activity.
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PMID:Cyclic nucleotide hydrolysis in the thyroid gland. General properties and key role in the interrelations between concentrations of adenosine 3':5'-monophosphate and guanosine 3':5'-monophosphate. 1 74

An understanding of the physiology of vascular smooth muscle and knowledge of the reaction of such muscle to certain drugs are essential for the development of a means of treating cerebral arterial spasm. The role of cyclic nucleotides in vascular smooth muscle activity is reviewed and possible therapeutic approaches are listed. Probably the safest and most effective treatment would be 1) stimulation of the adenyl cyclase-cyclic adenosine monophosphate system by a beta(2)-adrenergic drug combined with 2) inhibition of the phosphodiesterase system.
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PMID:A review of recent advances in vascular smooth muscle pharmacology. 1 4

It was found that the newly-available compound, bis-(4-methylumbelliferyl) phosphate, could be used as a substrate for the pig platelet surface membrane-associated phosphodiesterase activity, usually assayed with bis-(p-nitrophenyl) phosphate. This enzyme activity is distinct from the phosphodiesterase activity towards 5'-dTMP-P-nitrophenyl ester, which is probably associated with intracellular membrane structures in platelets. Consequently, the use of the 4-methylumbelliferyl derivative as substrate for the phosphodiesterase activity provides a sensitive, fluorimetric assay for this marker enzyme of the platelet surface membrane.
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PMID:Bis-(4-methylumbelliferyl) phosphate as a substrate for the surface membrane-associated phosphodiesterase activity of pig platelets. 1 36

The understanding of the properties of adrenergic receptors and modification of ring and the N-alkyl side chain constituents have resulted in adrenergic agents with a high degree of specificity for the lung and few cardiac and central nervous system stimulating problems. These agents are useful by aerosol and oral routes, alone and in addition to theophylline for asthma. Theophylline, which acts to increase cyclic AMP by inhibition of phosphodiesterase and beta 2 adrenergic agents which increase cyclic AMP by stimulating adenylate cyclase, are the mainstays of asthma therapy. Therapy is usually begun with theophylline. Persistent symptoms with adequate theophylline levels (10-20 mug/ml) indicates the need for a beta 2 adrenergic agent by aerosol or orally as a supplement. Occasional patients will not tolerate theophylline in any preparation and can be treated with beta 2 adrenergic agents with success. The future holds great promise for improved and safer beta 2 adrenergic agents which will offer the physician a more effective means of treating asthma.
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PMID:Treatment of asthma with theophylline and beta adrenergic agents. 1 64

In order to characterize age differences in the lipolytic effect of catecholamines on tests of subcutaneous adipose tissue of test persons aged from 0.1 to 10 years, from 20 to 40 years, and from 60 to 75 years the influence of propranolol, phentolamine and theophyllin on the release of glycerol by isoprenalin and adrenalin was investigated. Propranolol (10(8) and 10(5) mol/1) inhibits the lipolysis in the adipose tissue of all age groups stimulated by isoprenalin (10(6)and 10(5) mol/1). The following Ki-values were calculated: 2x10(6) mol/1in the tissue of adults, 0.5 x 10(6) mol/1 in the infantile adipose tissue, 0.2 X 10(6) mol/1 in the tissue of old persons. Phentolamine (10(5) mol/1) increases the lipolytic effect of adrenalin (10(5) mol/1), there are no age differences. Theophyllin (10 (2) mol/1) increases the release of glycerol induced by isoprenalin (10(5) mol/1) in infantile and adult adipose tissue, however, it has no influence on them in the adipose tissue of old man. The findings suggest the higher sensitivity of the fat cells of the ageing organism to beta-adrenergics underlies a higher affinity of the adrenergics to the specific beta-adrenoceptors in the cytoplasm membrane of the adipocytes. The more intensive lipid mobilization in old age by beta-adrenergics is explained by a low activity of the cAMP-phosphodiesterase of the fat cells and by the higher and possibly longer lasting increase of intracellular cAMP in this age group.
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PMID:[Age-dependence of catecholamine effects in man. IV. Effects of specific inhibitors on the lipolytic action of alpha and beta adrenergics]. 1 47

The Ca2+-dependent protein activator of 3':5'-cyclic adenosine monophosphate phosphodiesterase is shown to undergo a conformational transition upon binding of 2 mol of Ca2+/mol of activator. Circular dichroic studies indicate that Ca2+ induces an increase of 5-8% in alpha-helix content with a concomitant decrease in the amount of random coil. In the absence of Ca2+ and in the presence of [ethylenebis(oxoethylenenitrilo)]tetraacetic acid (EGTA), the protein contains 30-35% alpha helix, 50% random coil, and 15-20% beta-pleated sheat. Spectrophotometric titration indicates that the two tyrosyl residues have pK's of 10.4 and 11.9 and are therefore in different environments. The Ca2+-induced conformational change is accompanied by an increased exposure to protons of the partially exposed tyrosine, as shown by a shift in its pK from 10.4 to 10.). Increased solvation is also consistent with a negative difference spectrum at 287 and 279 nm as seen upon Ca2+ binding. Modification in the environment of all or some of the phenylalanine residues also is part of the conformational change accompanying Ca2+ binding. A new and rapid purification procedure which yields large amounts (25-30% yields) of homogenous protein activator and a direct and sensitive assay procedure for cAMP phosphodiesterase and its activator are also described.
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PMID:Conformational transition accompanying the binding of Ca2+ to the protein activator of 3',5'-cyclic adenosine monophosphate phosphodiesterase. 1 63


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