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)

To characterize the role of cyclic nucleotides in secretion of enzymes by the lacrimal gland, pieces of rat exorbital glands were perfused with (1) 8-bromoadenosine-3',5'-cyclic monophosphate (8 Br cyclic AMP), (2) 8-bromoguanosine-3',5'-cyclic monophosphate (8 Br cyclic GMP), (3) forskolin, a stimulator of adenylate cyclase activity, (4) 3-isobutyl-1-methylxanthine (IBMX), an inhibitor of phosphodiesterase activity, or (5) carbachol, a cholinergic agonist. As a measure of enzyme secretion, timed collections of the perifusate effluent were analysed for peroxidase, an enzyme secreted by the lacrimal gland. Control peroxidase secretion was 0.3-0.9 (u./min per milligram protein). Peroxidase secretion was stimulated by 8 Br cyclic AMP (1 mM), but not by 8 Br cyclic GMP (1 mM). A 2-fold increase was detected. Peroxidase secretion was also stimulated by forskolin (60 microM), IBMX (1 mM), and the cholinergic agonist carbachol, which all stimulated peroxidase secretion 2-or 3-fold. The effect of maximally effective concentrations of IBMX (1 mM) and carbachol (0.1 mM) on secretion was additive. Finally, Ca2+ depletion in the presence of EGTA (1 mM) inhibited both IBMX-and carbachol-induced secretion by 45% and 60% respectively. We conclude that cyclic AMP, but not cyclic GMP, can stimulate lacrimal gland enzyme secretion. Cyclic AMP appears to utilize a pathway separate from but convergent with cholinergic agonists.
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PMID:Cyclic nucleotide-dependent enzyme secretion in the rat lacrimal gland. 620 48

The biochemical properties of polymorphonuclear neutrophils from blood and peritoneal exudates of rabbits were compared. All enzymes measured showed almost identical activities in both types of cells, except for alkaline phosphodiesterase, the activity of which was seven times higher in peritoneal neutrophils. During phagocytosis, blood and peritoneal beta-glucuronidases were released in very similar fashions. Lysozyme, one of the enzymes concerned with killing of bacteria, as well as beta-glucuronidase, showed the same releasing pattern in both types of cells, but peroxidase was hardly released. Although superoxide anion generation in peritoneal neutrophils was two times higher than superoxide generation in blood neutrophils, phagocytic and bactericidal activities were almost the same in blood and peritoneal neutrophils. Blood neutrophils were more resistant to hypotonic lysis than were peritoneal neutrophils. These results show that there are no distinct differences in enzymatic and functional properties between blood and peritoneal polymorphonuclear neutrophils, except for alkaline phosphodiesterase activity, superoxide anion production, and osmotic fragility.
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PMID:Biochemical properties of polymorphonuclear neutrophils from venous blood and peritoneal exudates of rabbits. 626 Jun 50

In exorbital lacrimal glands, pentoxifylline (a methylxanthine) induces labeled protein secretion in a dose-related manner: the half-maximal and maximal stimulations are at 4 and 10 mM, respectively. In the presence of papaverine (10(-5) M), a phosphodiesterase inhibitor, labeled protein discharge is strongly stimulated by isoproterenol, via beta-adrenergic receptors: the maximal response is at 10(-6) M. l-Propranolol specifically inhibits the secretory stimulation to isoproterenol in a dose-related manner: for 5 X 10(-6) M isoproterenol in the presence of 10(-5) M papaverine, the half-maximal and maximal inhibitions are at 3 X 10(-7) and 10(-5) M, respectively. The beta-adrenergic response is mimicked by the adenosine 3',5'-cyclic monophosphate (cAMP) analogue dibutyryl cAMP (DBcAMP) at a 10(-3) M concentration. The time course of labeled protein secretion induced by pentoxifylline, DBcAMP, and isoproterenol shows a latency. In the presence or absence of extracellular calcium, pentoxifylline and isoproterenol immediately increase the cAMP intracellular level. Extracellular calcium omission increases the observed latency and also affects the maximal rate of protein secretion. As opposed to the cholinergic agonist, pentoxifylline has only a slight but sustained effect on 45Ca efflux, whereas isoproterenol has none. These data suggest that labeled protein secretion, such as that of peroxidase, can also be stimulated in rat exorbital lacrimal gland, through beta-adrenergic receptors; in the stimulation evoked by a beta-adrenergic agonist, DBcAMP, or methylxanthine, calcium could play a key role.
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PMID:Protein secretion induced by isoproterenol or pentoxifylline in lacrimal gland: Ca2+ effects. 632 Jun 58

This study employs the technique of electrical field stimulation (EFS) to characterise the effects of endogenous neurotransmitters on protein secretion in the in vitro pig lacrimal gland. The effects of exogenous applications of neurotransmitters on protein output and peroxidase secretion were also investigated for comparative purposes. EFS evoked frequency-dependent (5-20 Hz) increases in protein secretion. The EFS-evoked protein output was abolished with the nerve blocking drug tetrodotoxin (10(-6) M, TTX). Elevated potassium (100 mM KCl) can stimulate protein output in the presence of TTX. Exogenous application of either acetylcholine (ACh, 10(-9)-10(-4) M) or noradrenaline (NA, 10(-8)-10(-4) M) can also result in protein secretion, but they have no detectable effect on peroxidase secretion. In the presence of the cholinergic antagonist, atropine (10(-5) M) the EFS-induced protein output was reduced but not abolished. This atropine-resistant and non-cholinergic nerve-mediated component was further reduced in the combined presence of atropine, phentolamine, and propranolol (all 10(-5) M). When vasoactive intestinal polypeptide (VIP) receptor antagonist (10(-6) M [4-Cl-D-Phe6-Leu17]-VIP) was combined with the cholinergic and adrenergic antagonists, EFS caused a small but detectable increase in protein output. Exogenous application of either 10(-9) M VIP or 10(-9) M neuropeptide-Y (NPY) resulted in protein secretion. Combination of both VIP and NPY only induced an additive effect on protein output. Theophylline (10(-4) M), a phosphodiesterase inhibitor, evoked a small increase in protein output and had no significant effect on the secretory responses elicited by either VIP or NPY. In contrast, theophylline potentiated the non-cholinergic, non-adrenergic EFS-induced protein secretion. The results indicate that protein secretion from the porcine lacrimal gland may be controlled by cholinergic, adrenergic and non-cholinergic, non-adrenergic nerves. The peptidergic neurotransmitters may be VIP and other related neuropeptide(s). In addition to these neurophysiological studies, our results confirm previous findings that the porcine lacrimal nerves contain abundant quantity of NPY and VIP.
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PMID:Control of porcine lacrimal gland secretion by non-cholinergic, non-adrenergic nerves: effects of electrical field stimulation, VIP and NPY. 920 41

The first evidence that higher plants contain annexins was presented in 1989. Since that time, annexins have been purfied and characterized from a variety of plant sources. Analyses of the deduced proteins encoded by annexin cDNAs indicate that the majority of these plant annexins possess the characteristic four repeats of 70 to 75 amino acids and possess motifs proposed to be involved in Ca2+ binding. Like animal annexins, plant annexins bind Ca2+ and phospholipids and are abundant proteins, but there are indications that the number of distinct plant annexin genes may be considerably fewer than that found in animals. Regarding function, a number of studies show that various members of the annexin family of plants may play roles in secretion and/or fruit ripening, show interaction with the enzyme callose (1.3-beta-glucan) synthase, possess intrinsic nucleotide phosphodiesterase activity, bind to F-actin, and/or have peroxidase activity.
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PMID:Structures and functions of annexins in plants. 923 Sep 34

YM976 is a novel and specific phosphodiesterase 4 inhibitor. In our previous report, we indicated that YM976 has less emetogenicity, a major adverse effect of PDE4 inhibitors, than rolipram. In the present study, we examined the antiasthmatic effects of YM976 in guinea pigs. YM976 orally administered exhibited inhibition of antigen-induced bronchoconstriction, airway plasma leakage, airway eosinophil infiltration, and airway hyperreactivity (AHR), with ED(50) values of 7.3, 5.7, 1.0, and 0.52 mg/kg, respectively. Rolipram also dose dependently suppressed these responses. Prednisolone suppressed eosinophil infiltration and AHR, whereas it failed to inhibit bronchoconstriction and plasma leakage. Theophylline moderately suppressed bronchoconstriction and edema, but neither eosinophil infiltration nor AHR. YM976 suppressed the peroxidase activity in the bronchoalveolar lavage fluid, and elevated the intracellular peroxidase activity and cAMP contents of infiltrated cells, suggesting that YM976 inhibited not only the infiltration but also the activation of leukocytes. In vitro studies revealed that YM976 potently suppressed eosinophil activation (EC(30) = 83 nM), and exerted a little relaxation on LTD(4)-precontracted tracheal smooth muscle (EC(50) = 370 nM). Rolipram exhibited a potent tracheal relaxation activity (EC(50) = 50 nM). In vivo studies indicated that the inhibitory effect of YM976 on LTD(4)-induced bronchospasm was marginal even at 30 mg/kg p.o., although rolipram significantly inhibited the bronchospasm at the same dose. These results suggested that YM976, unlike rolipram, showed the inhibition of antigen-induced airway responses due to anti-inflammatory effects, but not to direct tracheal relaxation. In conclusion, YM976 may have potential therapeutic value in the treatment of asthma through its anti-inflammatory activities.
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PMID:Antiasthmatic effect of YM976, a novel PDE4 inhibitor, in guinea pigs. 1125 41

Calmodulin-binding proteins are involved in numerous cellular signaling pathways. The biotinylated-calmodulin overlay is a nonradioactive method widely used to detect calmodulin-binding proteins in tissue and cell samples. This method has several limitations; therefore, we developed a nonradioactive calmodulin-binding protein detection overlay using an S-tag-labeled calmodulin fusion protein. An expression system was used to generate a calmodulin fusion protein with an S-tag label, a 15 amino acid sequence that binds to a 105 amino acid S-protein. The S-protein is conjugated to horseradish peroxidase for final detection with a chemiluminescent substrate. The S-tag calmodulin was compared to purified calmodulin and biotinylated calmodulin in a calmodulin-dependent phosphodiesterase assay. The results of the calmodulin-dependent phosphodiesterase assay indicate that S-tag calmodulin induces higher phosphodiesterase activity than biotinylated calmodulin and lower activity than purified calmodulin. A comparison of the biotinylated and S-tag calmodulin overlay assays indicate that S-tag calmodulin is more sensitive than biotinylated calmodulin in the detection of calcineurin, a known calmodulin-binding protein. The overlay assay results also indicate that the S-tag calmodulin and biotinylated calmodulin detect similar calmodulin-binding proteins in colon epithelial cells. In conclusion, the S-tag calmodulin overlay assay is a consistent, sensitive, and rapid nonradioactive method to detect calmodulin-binding proteins.
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PMID:Calmodulin-binding protein detection using a non-radiolabeled calmodulin fusion protein. 1135 39

Insulin resistance is associated with vascular disease. Physiological concentrations of insulin inhibit cultured vascular smooth muscle cell (VSMC) contraction and migration by increasing nitric oxide (NO)-stimulated cGMP accumulation. The failure to do so in insulin-resistant states may aggravate vascular disease. We sought to determine the mechanism of insulin's increase in cGMP accumulation. Isobutylmethylxanthine, an inhibitor of phosphodiesterase activity, inhibited the decline in cGMP levels measured by immunoassay in cGMP-loaded cultured rat aortic VSMCs, but 1 nmol insulin did not. Thus, insulin's increase in cGMP accumulation is due to stimulated production, not inhibited hydrolysis and/or efflux. Insulin, which increases the NADH/NAD+ ratio in these cells, stimulated superoxide anion (O2-) accumulation measured by lucigenin luminescence to 256+/-25% (P<0.05) by a process that was blocked by the NADH oxidase inhibitor diphenyliodonium (DPI) and enhanced by the superoxide dismutase inhibitor diethyldithiocarbonate (DETCA). Insulin also stimulated hydrogen peroxide (H2O2) accumulation measured by horseradish peroxidase/luminol luminescence to 221+/-22% (P<0.05) by a DETCA-sensitive mechanism. H2O2 (100 micromol/L) in the absence of insulin increased NO-stimulated cGMP accumulation to 151+/-11% (P<0.05). Insulin alone increased NO-stimulated cGMP accumulation to 183+/-17% (P<0.05), and this was blocked by either DPI or DETCA. We conclude that insulin increases NADH oxidase-derived O2- production in cultured rat VSMCs. This did not cause the expected scavenging of NO resulting in the reduction of NO-stimulated guanylate cyclase activity, but enough O2- was metabolized to H2O2 to increase overall NO-stimulated cGMP production.
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PMID:Insulin-stimulated hydrogen peroxide increases guanylate cyclase activity in vascular smooth muscle. 1296 80

Calmodulin (CaM), a key Ca(2+) sensor in eukaryotes, regulates diverse cellular processes by interacting with many proteins. To identify Ca(2+)/CaM-mediated signaling components, we screened an Arabidopsis expression library with horseradish peroxidase-conjugated Arabidopsis calmodulin2 (AtCaM2) and isolated a homolog of the UBP6 deubiquitinating enzyme family (AtUBP6) containing a Ca(2+)-dependent CaM-binding domain (CaMBD). The CaM-binding activity of the AtUBP6 CaMBD was confirmed by CaM mobility shift assay, phosphodiesterase competition assay and site-directed mutagenesis. Furthermore, expression of AtUBP6 restored canavanine resistance to the Deltaubp6 yeast mutant. This is the first demonstration that Ca(2+) signaling via CaM is involved in ubiquitin-mediated protein degradation and/or stabilization in plants.
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PMID:Arabidopsis ubiquitin-specific protease 6 (AtUBP6) interacts with calmodulin. 1598 37

Although the structure of an enzyme is often depicted as static, it is dynamic. Hence, a population of chemically identical enzymes has not one, but a distribution of structures at any moment in time. Does this have an effect on the activity of the enzyme? This article reviews experiments designed to test the hypothesis that this distribution of structures results in a distribution of enzyme activities. The experiments reviewed here use different enzymes, falvin adenine dinucleotide, beta-galactosidase, alkaline phosphatase, exonuclease I, lactate dehydrogenase I, alpha-chymotrypsin, the 20S proteasome, and horseradish peroxidase. All experiments come to the same conclusion, when measured individually, apparently identical enzymes show a distribution in rates of activity.
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PMID:Diversity in the activity of individual enzymes. 1637 26


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