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 Ca2+-dependent ryanodine binding site of rabbit cardiac sarcoplasmic reticulum is solubilized by treatment with 20 mM CHAPS detergent and 1 M NaCl for 30 min at 0 degrees C. Ca2+ added at 5 microM enhances binding, at 0.5 mM increases both the affinity and number of [3H]ryanodine binding sites, while at 10 mM only the number of binding sites is increased. Mg2+ up to 1 mM does not significantly affect [3H]ryanodine binding. Radioligand binding is strongly enhanced by all alkali metal chlorides except LiCl. NaCl increases the rate of association of the ligand and the affinity of the binding site but does not influence the dissociation. NaCl and CaCl2 enhance the thermal stability of the [3H]ryanodine-binding protein. Thiol groups are essential for [3H]ryanodine binding. Ruthenium red and Cd2+ inhibit binding, while theophylline is stimulatory at low (micromolar) Ca2+ concentrations by a mechanism other than phosphodiesterase inhibition. Gel permeation chromatography establishes that the ryanodine binding protein is localized only in the high molecular mass fraction (greater than 669 kDa). Polyacrylamide gel electrophoresis of the proteins following treatment with SDS and 2-mercaptoethanol indicates that more than 90% are of low molecular mass (34-70 kDa) and that two stain blue with Stains-all as expected of Ca2+-binding proteins.
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PMID:Ca2+-dependent ryanodine binding site: soluble preparation from rabbit cardiac sarcoplasmic reticulum. 376 53

Effects of nonspecific smooth muscle relaxants, papaverine and Aspaminol (1,1-diphenyl-3-piperidinobutanol hydrochloride) on Ca-uptake by a microsomal fraction and mechanical activity in the rabbit taenia coli were studied. Papaverine which inhibits cyclic AMP phosphodiesterase increased Ca-uptake by the microsomal fraction in a concentration of 10(-5) M but not in a concentration of 10(-4) M. Potentiation of Ca-uptake by papaverine is considered to be due to the increase of cyclic AMP as the results of the inhibition of phosphodiesterase. Aspaminol which is found to have little inhibitory action on phosphodiesterase activity inhibited Ca-uptake by the microsomal fraction. This inhibition by Aspaminol was abolished by the increase of Ca-concentration in the reaction medium. Non-competitive antihistaminic activity of Aspaminol was considerably reduced by an increase of external Ca-concentration, while the increase of external Ca-concentration slightly decreased antihistaminic activity of papaverine. Furthermore, contraction of KCl-depolarized taenia coli induced by CaCl2 was inhibited competitively by Aspaminol and noncompetitively by papaverine. These results suggest that Aspaminol competes with Ca ions at a surface site of muscle membrane concerned with Ca-uptake process, thus decreasing the supply of Ca ions to the contractile elements and that papaverine may have inhibitory actions on Ca-uptake by the microsomal fraction in addition to stimulatory action which seems to be mediated through cyclic AMP. These actions on Ca-uptake may induce smooth muscle relaxation.
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PMID:Effects of nonspecific smooth muscle relaxants on calcium-uptake by microsomal fraction and their inhibitory action in rabbit taenia coli. 611 Jul 16

The effect of cyclic nucleotide analgoues upon the immediate induction of the guinea pig acrosome reaction (AR) was studied. Dibutyryl (dB) CGMP and 8-bromo-cGMP, when added to sperm suspensions after varying periods of preincubation in glucose-free BWW medium (NaCl 94.59 mM, KCl 4.7 mM, CaCl2 1.71 mM, KH2PO4 1.19 mM, MgSO4 1.19 mM, NaHCO3 25.07 mM, pyruvate 0.25 mM, lactate 21.58 mM, and bovine seru albumen 1 g/liter), induced the AR in a large proportion of spermatozoa relative to controls. The proportion of ARs induced upon the addition of dB cGMP or 8-bromo-cGMP (10mM) at 1 h was equivalent to that obtained after a 5-h incubation in glucose-free BWW alone. The effect of cGMP analogues was concentration dependent over the tested range of 2-12 mM (less than 1-20%). The simultaneous addition if imidazole (10 mM), a cAMP phosphodiesterase stimulator, potentiated the effect (imidazole + 12 mM 8-bromo-cGMP: 73%). cAMP analogues were without effect. The presence of extracellular Ca++ was required, and it is suggested that a rise in the cGMP/CAMP ratio triggers Ca++ influx and the AR.
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PMID:Induction of the acrosome reaction in guinea pig spermatozoa by cGMP analogues. 624 66

Agents known to increase cAMP levels in the myocardium were infused subepicardially (focal infusion, 10 microliter/min) in open-chested pigs. Infusion of noradrenalin (NA), adrenalin (10(-5) M each) or isoproterenol (10(-6) M) in the presence of Ca2+ (2.5 . 10(-3) M) consistently produced ventricular tachycardia (VT) within 60 s. This tachycardia could be mimicked by electrical stimulation of the infusion area. The NA/CA2+-VT could be maintained for 30 min and was readily reversible after stopping the infusion. Infusion of N6, O2'-dibutyryl-cAMP or N6-monobutyryl-cAMP (5 . 10(-2) M each) produced long-lasting VT within 10-20 min. VT was also induced by infusion of 8-Br-cAMP (5 . 10(-2) M) together wit the phosphodiesterase inhibitor Ro 7-2956 (5 . 10(-4) M) while infusion of the components alone had no such effect. The NA/Ca2+-VT was abolished by calcium antagonists [isoptin, D 600 (10(-4) M each), MnCl2 (5 . 10(-4) M] and beta-adrenoceptor blocking agents [propranolol (10(-4) M), pindolol (10(-6) M)], but was not suppressed by tetrodotoxin (up to 10(-5) M). Infusion of 5 x 10(-2) M N6-monobutyryl-2'-deoxy-cAMP, 2.5 x 10(-3) M CaCl2/0.9% NaCl or 10(-1) M Na-butyrate did not precipitate VT. Tissue analysis showed that myocardial cAMP was increased at the infusion site when the NA/Ca2+-VT ensued. It is concluded that the catecholamine-cAMP-Ca2+ system may play an important role in the initiation and perpetuation of VT, possibly by producing automaticity in ventricular fibres via slow Ca2+ channels.
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PMID:Catecholamine-cyclic-AMP-Ca+-induced ventricular tachycardia in the intact pig heart. 626 77

Calmodulin, a calcium-dependent modulator protein, is known to mediate a great number of Ca++-dependent processes in various tissues. Although it was originally described as a protein activator of cyclic nucleotide phosphodiesterase, the sensitivity of phosphodiesterases to this compound are suggested to be variable from tissue to tissue. In order to determine whether there was calmodulin-like activity in pig skin epidermis and to see its relationship to epidermal phosphodiesterase, we used an established calmodulin deficient phosphodiesterase system prepared from bovine heart. Calmodulin deficient phosphodiesterase prepared from bovine heart was markedly stimulated by the addition of pig skin (epidermal) boiled extract in the presence of calcium. Boiled skin extract alone had only little phosphodiesterase activity by itself. This effect of boiled skin extract on bovine heart phosphodiesterase was inhibited by the addition of EGTA, a divalent metal ion chelator of relative Ca++ specificity. At a fixed concentration of EGTA, increasing the Ca++ concentration counteracted the effect of EGTA. Pure pig skin epidermis (separated by trypsinization, NaBr, CaCl2-sucrose or NH4Cl treatment) was also shown to have heat-stable calmodulin activity. In contrast to the bovine heart phosphodiesterase, epidermal phosphodiesterase was only partially inhibited when Ca++ was removed by EGTA. The addition of boiled skin extract on the crude extract of epidermal phosphodiesterase had minimal effect on the enzyme activity. Overall results indicate that although pig skin epidermis contains significant amount of calmodulin, the regulation of phosphodiesterase may not be the main biological activity of epidermal calmodulin.
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PMID:Pig skin epidermal calmodulin: effect on calmodulin deficient phosphodiesterase. 627 75

The level of adenosine 3',5'-monophosphate (cyclic AMP) in the eggs of the sea urchin, Anthocidaris crassispina, was found to change periodically after fertilization. The minimum and maximum levels of cyclic AMP were 1.0 X 10(-7)M and 1.5 X 10(-6)M, respectively. The activity of adenylate cyclase in a 105 000 X g precipitate reached a plateau at 20 min after fertilization and stayed constant for at least 2 h. It was also found that 1.0 mM CaCl2 increased the activity of adenylate cyclase in the same precipitate from unfertilized eggs. In contrast, phosphodiesterase activity changed periodically and correlated with cyclic AMP levels in the eggs. Up to a concentration of 1.5 X 10(-6)M cyclic AMP, phosphodiesterase activity was low, but it became activated when the level of cyclic AMP rose beyond this level. These results indicate that the change in the intracellular level of cyclic AMP is regulated mainly by the change in phosphodiesterase activity.
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PMID:The periodic change in adenosine 3',5'-monophosphate concentration in sea-urchin eggs. 628 94

The effects of divalent cations on the induction of phosphodiesterase [EC 3.1.4.17] by cyclic adenosine 3',5'-monophosphate (cyclic AMP) were studied in Dictyostelium discoideum. When cells were incubated with 1 mM ethylene glycol-bis(beta-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA) in 20 mM Tris-HCl buffer, pH 7.5, for 2 h, the induction of cellular phosphodiesterase was inhibited by about 80%, and that of extracellular phosphodiesterase by about 65%. When cells were incubated with 1 mM EGTA for 1 h, 2 mM CaCl2 was added and the cells were further incubated for 1 h, the activities of cellular and extracellular phosphodiesterases were increased about 5 and 2.5 times, respectively, compared with those in the EGTA-inhibited cells. Although various other kinds of divalent cations were also studied, Ca2+ had the greatest effect on the induction. These results suggest that Ca2+ may participate in the induction of phosphodiesterase, and thus in the regulation of the development of the cellular slime mold.
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PMID:Participation of calcium in the induction of phosphodiesterase by cyclic adenosine 3',5'-monophosphate in Dictyostelium discoideum. 629 92

1. The activities of cyclic cytidine 3',5'-monophosphate (cCMP) phosphodiesterase in normal rat liver and host liver (bearing hepatoma 5123 t.c.(h)) were compared with those of three Morris hepatomas of varying growth rates. 2. The results show that the order of enzyme activity was as follows: normal liver = host liver greater than 7794A (slow growth rate) greater than 5123 t.c.(h) (intermediate growth rate) greater than 7800 (fast growth rate). 3. The enzyme had a pH optimal value of about 7.0 and an apparent Km for cCMP about 2.8 mM; its activity was slightly affected by the presence of calmodulin (100 micrograms/ml) and/or CaCl2 (100 microM), but showed variable responses to other cations (La3+, Mg2+, Mn2+, Zn2+, Fe2+, Na+ and K+).
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PMID:Decreased activities of cyclic cytidine 3',5'-monophosphate phosphodiesterase in Morris hepatomas having varying growth rates. 630 41

We have separated and characterized a Ca2+- and calmodulin-insensitive cyclic nucleotide phosphodiesterase from rat liver supernatant as well as an analogous enzyme from HTC hepatoma cells. Chromatography of rat liver supernatant on DEAE-cellulose in the presence and subsequently in the absence of 0.1 mM-CaCl2 resulted in the separation of two distinct phosphodiesterase activities, both of which preferentially hydrolysed cyclic GMP rather than cyclic AMP. One enzyme, E-Ib, was activated in the presence of Ca2+ and calmodulin, and the other, E-Ia, was not. The E-Ia enzyme, which did not bind to calmodulin-Sepharose, had Mr 325 000 and displayed anomalous kinetic behaviour [Km (cyclic GMP) 1.2 microM; Km (cyclic AMP) 15.4 microM]. The E-Ib enzyme, which bound to calmodulin-Sepharose in the presence of Ca2+, had Mr 150 000 and exhibited Michaelis-Menten kinetics for hydrolysis of cyclic GMP [Km (basal) 6.5 microM; Km (activated) 12.0 microM]. E-Ia activity was diminished by incubation with alpha-chymotrypsin and was unaffected by the action of a rat kidney lysosomal proteinase. Partial hydrolysis of E-Ib enzyme by alpha-chymotrypsin or the kidney proteinase resulted in irreversible activation of the enzyme. The E-I enzyme isolated from HTC hepatoma cells was similar to the rat liver E-Ia enzyme in many respects. Its apparent Mr was 325 000. Its activity was unaffected by calmodulin in the presence of Ca2+ or by incubation with the kidney proteinase, and was decreased by digestion with alpha-chymotrypsin. Unlike the liver E-Ia enzyme, however, the hepatoma enzyme exhibited normal kinetic behaviour, with Km (cyclic GMP) 3.2 microM. Although HTC cells contain two other phosphodiesterases analogous to those in rat liver and a calmodulin-like activator of phosphodiesterase, no calmodulin-sensitive phosphodiesterase was detected.
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PMID:Ca2+-independent cyclic GMP phosphodiesterases from rat liver and HTC hepatoma cells. 631 Nov 63

Enzymatic activity which hydrolyzes diadenosine 5',5"'-P1,P4-tetraphosphate (Ap4A) yielding ADP has been identified in extracts of eubacteria, Escherichia coli and Acidaminococcus fermentans, and of a highly thermophilic archaebacterium, Pyrodictum occultum. Specific Ap4A (symmetric) pyrophosphohydrolase from Escherichia coli K12 has been purified almost 400-fold. The preparation was free of phosphatase, ATPase, phosphodiesterase, AMP-nucleosidase, and adenylate kinase. The Ap4A pyrophosphohydrolase molecular weight estimated by gel filtration is 27,000 +/- 1,000. Activity maximum is at pH 8.3. The Km value computed for Ap4A is 25 +/- 3 microM. The sulfhydryl group(s) is essential for enzyme activity. Metal chelators, EDTA, and o-phenanthroline, inhibit Ap4A hydrolysis; I0.5 values are 3 and 50 microM, respectively. Co2+ is a strong stimulator with an almost 100-fold increase in rate of Ap4A hydrolysis and a plateau in the range of 100-500 microM Co2+, when compared with the nonstimulated hydrolysis. Other transition metal ions, Mn2+, Cd2+, and Ni2+, stimulate by factors of 8, 3.5, and 3.5, respectively, with optimal concentrations in the range 200-500, 2-5, and 4-8 microM, respectively. Zn2+, Cu2+, and Fe2+, up to 30 microM, are without effect and they inhibit at higher concentrations. Mg2+ or Ca2+, in the absence of other divalent metal ions, are weak stimulators (1.5-fold stimulation occurs at 1-2 mM concentration), but act synergistically with Co2+ at its suboptimal concentrations. Stimulation in the presence of 10 microM Co2+ and either 1 mM MgCl2 or CaCl2 increases up to 75-fold. The same degree of synergy is found at 10 microM Co2+ and either 2-5 mM spermidine or 0.5-1.5 mM spermine. Besides Ap4A, bacterial Ap4A pyrophosphohydrolase hydrolyzes effectively Ap5A and Gp4G, and, to some extent, p4A, Ap6A, and Ap3A yielding in each case corresponding nucleoside diphosphate as one of the products.
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PMID:Catabolism of diadenosine 5',5"'-P1,P4-tetraphosphate in procaryotes. Purification and properties of diadenosine 5',5"'-P1,P4-tetraphosphate (symmetrical) pyrophosphohydrolase from Escherichia coli K12. 631 72


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