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)

Release of the neuropeptide egg-laying hormone (ELH) from Aplysia bag cell neurons augments the endogenous bursting pacemaker activity of neuron R15. We have studied the ionic mechanisms underlying the effect of ELH in voltage-clamped R15 neurons. Both electrical discharge of the bag cells, which releases endogenous ELH, and application of synthetic ELH on cell R15 result in an increase in two discrete ionic currents. One of these currents activates with hyperpolarization, reverses near the K+ equilibrium potential, is sensitive to the external K+ concentration, and is blocked by addition of 5 mM Rb+ or 1 mM Ba2+ to the bathing medium. This current appears to be identical to the inwardly rectifying K+ current IR. The other current activates with depolarization and is blocked by replacement of external Ca2+ with Co2+ or Mn2+. This current appears to be a voltage-gated Ca2+ current ICa. Both ICa and IR in R15 have previously been shown to be enhanced by the neurotransmitter serotonin, acting via intracellular cyclic AMP. We now report that increasing cyclic AMP in R15, by applying either serotonin or the adenylate cyclase activator forskolin together with a phosphodiesterase inhibitor, mimics and occludes the action of ELH on neuron R15. Furthermore, application of ELH increases the cyclic AMP content of single R15 neurons, as measured by radioimmunoassay. Finally, the effects of ELH are potentiated by a phosphodiesterase inhibitor. These results suggest that ELH augments bursting activity in R15 by causing cyclic AMP-mediated increases in IR and ICa.
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PMID:Augmentation of bursting pacemaker activity by egg-laying hormone in Aplysia neuron R15 is mediated by a cyclic AMP-dependent increase in Ca2+ and K+ currents. 281 71

In GH4C1 cells, the calmodulin antagonist trifluoperazine (TFP) showed a dose-dependent, biphasic effect on the basal release of PRL. An inhibition of PRL release was observed with 15-50 mumol/l TFP, whereas a concentration of 100 mumol/l and above had a stimulatory effect. The increase in basal hormone release evoked by TRH (1 mumol/l) and high extracellular concentration of K+ (50 mmol/l) was eliminated by 30 mumol/l TFP. The stimulatory effect of 100 mumol/l TFP on basal hormone release was not affected by addition of TRH (1 mumol/l) or K+ (50 mmol/l). The Ca2+ antagonists Co2+ (5 mmol/l) and verapamil (100 mumol/l), and the Ca2+ chelator EgTA (4 mmol/l) abolished the stimulatory effect of TRH (1 mumol/l) and of K+ (50 mmol/l) on PRL release, whereas only Co2+ inhibited the stimulation caused by 100 mumol/l TFP. TFP (75 mumol/l) caused a transient increase in the concentration of cellular cAMP. Incubation of intact GH4C1 cells with TFP (75 mumol/l), had an inhibitory effect on both the low and the high affinity form of cAMP phosphodiesterase. Basal as well as TRH-stimulated adenyl cyclase activity were inhibited by TFP, and this effect was counteracted by addition of calmodulin.
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PMID:Effects of trifluoperazine on prolactin release and cyclic AMP formation and degradation in GH4C1 pituitary cells. 282 17

Phosphodiesterase I [EC 3.1.4.1] was purified from normal human urine in a highly purified state free from phosphodiesterase II, RNase, DNase I, DNase II, and phosphatase by column chromatographies of DEAE-Toyopearl, butyl-Toyopearl, Affi-Gel blue, and Sephadex G-150. The molecular weight of the enzyme was 1.9 x 10(5) and the pH optimum around 9.0 with p-nitrophenyl deoxythymidine 5'-phosphate as the substrate. The enzyme hydrolyzed the 3'-5' linkage of various dinucleoside monophosphates at approximately the same rate and the phosphodiester bonds of cyclic 3',5'-mononucleotides to produce mononucleoside 5'-phosphate. The enzyme also hydrolyzed ADP to 5'-AMP and Pi, ATP to 5'-AMP and PPi, and NAD+ to 5'-AMP and NMN. The enzyme activity was abolished by removal of metal ions with EDTA, and the metal-free enzyme was reactivated on the addition of Zn2+. The enzyme activity was also abolished by some reducing agents and the inhibition was reversed by Zn2+. The metal-free enzyme was less stable than the native enzyme, and Zn2+ and Co2+ restored the stability of the metal-free enzyme to the level of the native enzyme. The enzyme degraded oligonucleotides and high molecular nucleotides stepwise from the 3'-termini to give 5'-mononucleotides. The enzyme hydrolyzed single-stranded DNA more preferentially than double-stranded DNA. The enzyme also nicked superhelical covalently closed circular phi X174 DNA to yield first open circular DNA and then linear DNA.
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PMID:Phosphodiesterase I in human urine: purification and characterization of the enzyme. 282 85

The effects of Cd2+ on Ca2+-sensitive myosin ATPase activity were examined. In the absence of Ca2+, the Ca2+-dependent myosin ATPase activity was enhanced by Cd2+ to the same extent as with Ca2+ at concentrations ranging from 10(-6) to 10(-3) M. At 10(-2) M, however, no activation was observed. Zn2+, Co2+, and Sr2+ also activated the myosin ATPase. Sr2+ and Co2+ were less effective. Hg2+, Cr3+, and Cu2+ were essentially inactive. In the presence of below 10(-3) M Ca2+, the increase in the enzyme activity observed on the addition of Cd2+ was in addition to that caused by Ca2+ alone. The ability of metal ions to activate myosin ATPase was compared with that to activate calmodulin-dependent cAMP phosphodiesterase. The activating effects of the metal ions tested were in the order of Ca2+ greater than Cd2+ greater than Zn2+ greater than Co2+ greater than Sr2+ for Ca2+-sensitive myosin ATPase and Ca2+ greater than Cd2+ greater than Sr2+ greater than Zn2+ greater than Hg2+ greater than Co2+ for cAMP phosphodiesterase. Cd2+ activated both enzyme activities most efficiently among the metal ions tested except Ca2+. These results indicate that Cd2+ is able to substitute for Ca2+ in the case of Ca2+ dependent enzymes, regardless of whether or not calmodulin participates in the activating process.
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PMID:Enhancement of Ca2+-sensitive myosin ATPase activity by cadmium. 282 3

A study has been made of the action of the neuropeptide proctolin on the radiosodium efflux from single barnacle muscle fibers. Proctolin (10(-8) M) when applied externally causes stimulation of the Na efflux in unpoisoned and ouabain-poisoned fibers. The response is prompt in onset, reaches a peak in 15 min and decays slowly. The response of the ouabain-insensitive Na efflux to external proctolin is dose-dependent, the concentration threshold being less than 10(-10) M. The response to proctolin is dependent on external Ca2+ but not on Na+. (i) The response to proctolin is abolished by high external Mg2+, as well as by verapamil, Co2+, Cd2+ and WB-4101. (ii) The response is also abolished by preinjecting 0.5 M MgCl2 or 0.1 M EGTA. The calmodulin antagonists trifluoperazine and imipramine are without effect on the response to proctolin. (i) Adenylate cyclase agonists, e.g. forskolin, fail to augment the response to proctolin. (ii) Prior injection of the phosphodiesterase inhibitors 1-propyl-3-methyl-7-(5-hydroxyhexyl)-xanthine (PMX) or 1-isoamyl-3-isobutylxanthine (IAX) fails to augment the response to proctolin. (iii) Prior injection of protein kinase inhibitor is ineffective. The response to proctolin is significantly reduced in the presence of tyramine. Taken together, these results support the view that proctolin stimulates the ouabain-insensitive Na efflux by activating Ca2+ channels and that the cAMP-protein kinase system is not involved in this response.
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PMID:Stimulation by proctolin of the ouabain-insensitive sodium efflux in single barnacle muscle fibers. 286 54

Activation of alpha 1-adrenergic receptors increases [Ca+2]i and phosphatidylinositol phosphodiesterase (phospholipase C) activity in the pinealocyte. In this report the receptor involved in the stimulation of phospholipase C activity was further characterized, and the role of Ca2+ in this effect was investigated in some detail. Phospholipase C activity was estimated by measuring the production of [3H]inositol phosphates by [3H]inositol-labelled dispersed pinealocytes in suspension culture. Norepinephrine stimulated [3H]inositol monophosphate production severalfold; this was blocked by alpha 1-adrenergic antagonists, including prazosin, WB 4101, and phenoxybenzamine, but by neither an alpha 2- nor a beta-adrenergic antagonist, confirming that an alpha 1-adrenoceptor is involved in the regulation of phosphatidylinositol hydrolysis. Treatment with the Ca2+ chelator, EGTA, or with inorganic Ca2+ blockers, including Co2+, Mn2+, and La3+, reduced the norepinephrine-stimulated response, suggesting that the alpha 1-adrenergic stimulation of phospholipase C activity is Ca2+ dependent. However, phospholipase C activity was not increased by elevating intracellular Ca2+ with either the Ca2+ ionophore A23187 or with depolarizing concentrations of K+. These results indicate that although Ca2+ is necessary for alpha 1-adrenergic stimulation of phospholipase C activity, an increase in [Ca2+]i alone is not sufficient to stimulate the activity of this enzyme, and that effects which A23187 and depolarizing concentrations of K+ have on pineal function probably do not involve stimulation of phospholipase C activity.
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PMID:Permissive role of calcium in alpha 1-adrenergic stimulation of pineal phosphatidylinositol phosphodiesterase (phospholipase C) activity. 290 66

Micropressure ejection of serotonin (5-hydroxytryptamine, 5-HT) produced excitatory responses in the L14 ink motor neurons of Aplysia that depended on the site of application. Ejection of 5-HT onto the cell body produced a slow response that showed variability in voltage sensitivity between preparations. In contrast, ejection of 5-HT onto the neuropil underneath the cell body produced a response whose amplitude was consistently a linear function of the holding potential, reversing near the predicted potassium equilibrium potential. Subsequent analyses focused on this second response. The neuropil response induced by 5-HT had a linear current-voltage relationship (reversing at ca. -80 mV), was associated with a decrease in input conductance, and was sensitive to changes in the concentration of extracellular K+. Serotonin application in artificial seawater (ASW) containing 30 mM K+ produced a response that reversed close to the altered Nernst potential for K+. The 5-HT response did not appear to be due to secondary activation of interneurons or to depend primarily on extracellular Ca2+, since ejection of 5-HT onto cells bathed in ASW containing 30 mM Co2+ produced responses comparable to, although somewhat attenuated from, those observed in ASW. Serotonin responses similar to those produced in ASW were obtained after perfusing the ganglion with ASW containing Co2+, 4-aminopyridine (4-AP), and tetraethylammonium (TEA). This suggests that the 5-HT-sensitive current is separate from the Ca2+-activated, fast, and delayed rectifying K+ currents. The 5-HT response appeared to be mediated by changes in levels of cAMP. Bath application of the phosphodiesterase inhibitors IBMX (3-isobutyl-1-methylxanthine) or Ro 20-1724, or the adenylate cyclase activator forskolin mimicked the 5-HT response by producing a slow inward current associated with a decrease in membrane conductance. Alteration of cellular cAMP metabolism modulated the response to 5-HT. Exposure of the ganglion to low concentrations of either Ro 20-1724 or forskolin potentiated the 5-HT response. Higher concentrations of these agents largely blocked the response to subsequent 5-HT applications. Bath application of the 8-bromo derivative of either cAMP or cGMP produced a slow inward current associated with a decrease in membrane conductance in cells voltage clamped at the resting potential. Responses to 5-HT were blocked, however, after exposure to 8-bromo-cAMP, but not to 8-bromo-cGMP. These results suggest that 5-HT produces a voltage-independent decrease in a steady-state potassium conductance that may be mediated by cAMP.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Analysis of decreased conductance serotonergic response in Aplysia ink motor neurons. 298 53

All members of the Enterobacteriaceae possess distinct 5'-nucleotidases and cyclic phosphodiesterases (3'-nucleotidases) that can be differentiated from the acid and alkaline phosphatases and the acid sugar hydrolases. The nucleotidases and cyclic phosphodiesterases of the various Enterobacteriaceae are remarkably similar in properties. All of the 5'-nucleotidases hydrolyze 5'-nucleotides, adenosine triphosphate, and uridine diphosphoglucose. Their pH optimum is from 5.7 to 6.1. The cyclic phosphodiesterases hydrolyze 3'-nucleotides, cyclic phosphonucleotides, bis-(p-nitrophenyl)phosphate, and p-nitrophenylphosphate. Their pH optimum is from 7.2 to 7.8. For both enzymes, cobalt showed optimal metal stimulation. An intracellular protein inhibitor for the 5'-nucleotidase is present in all of the Enterobacteriaceae. No inhibitor of cyclic phosphodiesterase activity exists, although hydrolysis of both cyclic phosphonucleotides and 3'-nucleotides is inhibited by ribonucleic acid. Neither of the enzymes is subject to control by phosphate level or by catabolite repression. Of the other bacteria studied, only Haemophilus and Bacillus subtilis contained significant 3'- or 5'-nucleotidase activity.
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PMID:The 5'-nucleotidases and cyclic phosphodiesterases (3'-nucleotidases) of the Enterobacteriaceae. 496 71

A variety of chemical and electrophysiological evidence indicates that the onset of afterdischarge and the subsequent profound enhancement of spike broadening that occur in the bag cell neurons of Aplysia are related to an increase in adenosine 3',5'-monophosphate-(cAMP) dependent protein phosphorylation. We have now used a two-electrode voltage clamp to study the properties of isolated bag cell neurons in cell culture and their response to 8 benzylthio-cAMP (8BTcAMP) and N6-n-butyl 8BTcAMP. These membrane-permeant and phosphodiesterase-resistant cAMP analogs induce spontaneous discharge and spike broadening in both the intact bag cell cluster and isolated bag cell neurons in cell culture. The dominant inward current in these cultured cells was found to be the calcium current, Ica, which was abolished by Co2+ (20 mM) or Ni2+ (10 mM) and could be observed in Na+-free media. In a minority of cells (2 of 12), in normal ionic media, a transient inward current was observed that was unaffected by Co2+ and Ni2+ and probably represents a sodium current. The three characterized potassium currents, the delayed rectifying current IK, the calcium-dependent current IC, and the early transient current IA, distinguished by their differing pharmacological and voltage-activation properties, were present in all healthy cells. Three effects of the cyclic AMP analogs (0.5 mM) on the electrical properties of these cells were 1) the emergence of a region of negative slope resistance in the steady-state I-V relations, 2) a depression of the net sustained outward currents due to depolarizing commands, and 3) a marked reduction in IA. When outward currents had been largely suppressed using high concentrations of tetraethylammonium (TEA) ions (100-460 mM) no effects of the cyclic AMP analogs could be observed on peak inward currents using NA+ and Ca2+ or Ba2+ as carriers of inward current. At least part of these electrical effects of the cyclic AMP analogs could be accounted for by a depression of a delayed potassium current and the A current.
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PMID:A voltage-clamp analysis of currents underlying cyclic AMP-induced membrane modulation in isolated peptidergic neurons of Aplysia. 609 Jun 5

Quercetin is a naturally occurring flavonoid, chemically related to cromolyn. Quercetin has been shown to inhibit antigen- and mitogen-induced histamine release from rat mast cells and basophils of subjects with hay fever, to increase cyclic adenosine monophosphate (AMP) in Ehrlich ascites tumor cells and to inhibit phosphodiesterase and certain adenosine triphosphatase (ATPase) systems. We have studied the effect of quercetin on mouse T cell responses. When 5 x 10(-6) to 5 x 10(-5) M quercetin is present throughout either allogeneic mixed leukocyte culture (MLC) or cytotoxic T lymphocyte (CTL) assay culture, inhibition of in vitro CTL generation or effector function results, respectively (inhibition is 75-100% at 2 x 10(-5) M and 100% at 5 x 10(-5) M). Quercetin also inhibits concanavalin A-induced DNA synthesis. Addition of Cu2+ strongly blocks the effects of quercetin in all systems tested, in a concentration dependent fashion, while Mg2+ and Ca2+ have little or no effect and Mn2+ and Co2+ have a significant but slight blocking effect on quercetin-mediated inhibition of both CTL generation and function. In kinetic studies, evidence was obtained for the existence of a major quercetin-sensitive step in CTL induction, between 3 and 24 hr of the MLC.
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PMID:Quercetin inhibition of the induction and function of cytotoxic T lymphocytes. 621 17


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