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)

In order to compare the known morphological changes which occur during the postnatal development of the salivary glands in the rat with alterations in membrane function, we measured adenylate cyclase activity and its responses to sodium fluoride (NaF), norepinephrine, and isoproterenol in salivary gland membranes at various times after birth. In the parotid gland, basal enzyme activity did not change significantly during postnatal life, but fluoride-stimulated activity rose on day 15; A similar marked rise in activity stimulated by norepinephrine (0.02 mM) and isoproterenol (0.03 mM) was noted simultaneously. In the submandibular gland, basal adenylate cyclase activity was higher just after birth than at 25 days of life or in maturity. Fluoride-stimulated activity was 7 times higher than basal activity on day 1, greater than 10 times higher on day 25, and 30 times greater in the adult. The gland was as responsive to norepinephrine and isoproterenol on day 5 as it was on day 25 or in the mature animal, showing a two- to threefold increase over the basal enzyme value at each time point studied. Residual phosphodiesterase activity in the membranes was always negligible. The data demonstrate a time-dependent developmental change in the responsiveness of the parotid gland to norepinephrine and isoproterenol, which corresponds to the time when morphological maturation normally occurs. By contrast, in the submandibular gland, membrane-bound adenylate cyclase is fully developed at the time of birth.
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PMID:Postnatal development of adenylate cyclase in rat salivary glands: patterns of hormonal sensitivity. 16 27

Fluoride-stimulated adenylate cyclase is demonstrated inisolated tumor cells of transplantable rat pituitary tumor MtT-F4 in vitro. The intracellular cyclic adenosine 3':5'-monophosphate is lowered in the cells incubated in the presence of synthetic somatostatin. Contrary to the findings reported for normal pituitary, however, the immunoreactive growth hormone release does not change when either somatostatin or phosphodiesterase inhibitors are present in the incubation medium. The presence of dibutyryl cyclic adenosine 3':5'-monophosphate (5 mM) in the incubation medium does not change the rate of growth hormone release by isolated tumor cells.
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PMID:Effect of somatostatin on growth hormone release by MtT-F4 rat pituitary tumor in vitro. 19 84

Fat cell ghosts and homogenates of fat cells were used to study the influence of training on the regulatory system for lipolysis in adipose tissue of female rats. A training effect was identified from elevated succinate dehydrogenase activities in the soleus and plantaris muscles. Neither basal nor maximal (NaF-stimulated) adenylate cyclase activities per mg protein of fat cell ghosts were altered by training. Fluoride-stimulated adenylate cyclase activity per microgram DNA was lower in the trained than untrained group. Adenylate cyclase activities in response to norepinephrine expressed either on a per mg protein or per microgram DNA basis were lower (P less than 0.05) in fat cell ghosts from trained rats. Phosphodiesterase activity was higher (P less than 0.05) in fat cell ghosts from trained rats for cyclic AMP concentrations of 1--5.0 micrometer. The apparent Km's of phosphodiesterase were 1.19 and 2.0 micrometer of cyclic AMP for the untrained and trained groups, respectively (P less than 0.05). Protein kinase activity in the supernatant fraction of homogenates of fat cells was unchanged due to training. The overall effect of training was to blunt the system for cyclic AMP production in rat adipocytes. This may explain, at least partially, the lower plasma free fatty acid levels observed in trained compared to untrained persons during submaximal exercise.
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PMID:Effect of physical training on control mechanisms of lipolysis in rat fat cell ghosts. 19 25

3'-Fluoro-2',3'-dideoxythymidine 5'-(alpha-methylphosphonyl)-beta,gamma- diphosphate and 2'-deoxythymidine-5'-(alpha-methylphosphonyl)-beta, gamma- diphosphate have been synthesized. Both compounds are incorporated into DNA chains during catalysis by reverse transcriptases of human immunodeficiency (HIV) and avian myeloblastosis (AMV) viruses, DNA polymerase beta from rat liver, terminal deoxynucleotidyl transferase from calf thymus and (at a very low rate) is by E. coli DNA polymerase I, Klenow fragment. The first compound is a termination substrate while the second is capable of multiple incorporation into the DNA chains. For instance, reverse transcriptase catalysis resulted in the appearance of 8 residues of second compound. DNA polymerases alpha and epsilon from human placenta incorporated none of the above compounds into DNA chains, although an inhibition of DNA synthesis by both compounds was observed with all enzymes mentioned. The 3'----5'-exonuclease activity of DNA polymerase I, Klenow fragment, hydrolyzed DNA fragments containing phosphonomethyl internucleoside groups, while such DNA fragments were resistant to the E. coli exonuclease III.
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PMID:Formation of phosphonester bonds catalyzed by DNA polymerase. 137 65

Fluoride acts as a noncompetitive, strong inhibitor of (asymmetrical) Ap4A hydrolases (EC 3.6.1.17). The Ki values estimated for the enzymes isolated from seeds of some higher plants (yellow lupin, sunflower and marrow) are in the range of 2-3 microM and I50 for the hydrolase from a mammalian tissue (beef liver) is 20 microM. The anion, up to 25 mM, does not affect the following other enzymes which are able to degrade the bis(5'-nucleosidyl)-oligophosphates: Escherichia coli (symmetrical) Ap4A hydrolase (EC 3.6.1.41), yeast Ap4A phosphorylase (EC 2.7.7.53), yellow lupin Ap3A hydrolase (EC 3.6.1.29) and phosphodiesterase (EC 3.1.4.1). None of halogenic anions but fluoride affects the activity of (asymmetrical) Ap4A hydrolases. Usefulness of the fluoride effect for the in vivo studies on the Ap4A metabolism is shortly discussed.
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PMID:Fluoride is a strong and specific inhibitor of (asymmetrical) Ap4A hydrolases. 215 11

Treatment of washed, ejaculated bovine sperm with 30 mM sodium fluoride immobilized the cells in a characteristically rigid form. In cells metabolizing endogenous substrates, fluoride decreased respiration by about 60%, but did not inhibit the cells' ability to produce adenosine-5'-triphosphate (ATP) via oxidative phosphorylation and did not block access to endogenous substrates. Fluoride-immobilized sperm maintained maximal ATP titers for at least 60 min, but oligomycin treatment rapidly depleted ATP, indicating that ATP synthesis and metabolism was occurring in immobilized sperm. The putative phosphodiesterase inhibitor caffeine (2.5 mM) restored motility and increased respiration in fluoride-treated sperm, but 8-bromo-adenosine-3',5'-monophosphate (8-bromo-cAMP) did not, even though 8-bromo-cAMP stimulated respiration in control (untreated) sperm. Carboxyfluorescein analysis of the intracellular pH of untreated sperm indicated a normal pH of 6.3. Fluoride addition decreased the apparent intracellular pH slightly, but this effect was attributable to dilution. Caffeine did not change internal pH in untreated or fluoride-immobilized sperm. Fluoride did not appear to affect cAMP metabolism, but caffeine increased intracellular cAMP titers by about 35% in both untreated and fluoride-inhibited sperm. However, caffeine treatment did not mimic 8-bromo-cAMP, as analyzed by electrophoresis and autoradiography of sperm proteins labeled with 32P from endogenously generated [32P]ATP. Clearly, caffeine is not stimulating motility in fluoride-treated sperm by affecting the cyclic AMP system. Fluoride also inhibited motility in digitonin-permeabilized sperm by a mechanism that may have involved magnesium depletion, but caffeine had no stimulatory effect on either untreated or fluoride-immobilized, permeabilized sperm.
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PMID:Effects of fluoride and caffeine on the metabolism and motility of ejaculated bovine spermatozoa. 282 21

Fluoride activation of G proteins requires the presence of aluminium or beryllium and it has been suggested that AIF4- acts as an analogue of the gamma-phosphate of GTP in the nucleotide site. We have investigated the action of AIF4- or of BeF3- on transducin (T), the G protein of the retinal rods, either indirectly through the activation of cGMP phosphodiesterase, or more directly through their effects on the conformation of transducin itself. In the presence of AIF4- or BeF3-, purified T alpha subunit of transducin activates purified cyclic GMP phosphodiesterase (PDE) in the absence of photoactivated rhodopsin. Activation is totally reversed by elution of fluoride or partially reversed by addition of excess T beta gamma. Activation requires that GDP or a suitable analogue be bound to T alpha: T alpha-GDP and T alpha-GDP alpha S are activable by fluorides, but not T alpha-GDP beta S, nor T alpha that has released its nucleotide upon binding to photoexcited rhodopsin. Analysis of previous works on other G proteins and with other nucleotide analogues confirm that in all cases fluoride activation requires that a GDP unsubstituted at its beta phosphate be bound in T alpha. By contrast with alumino-fluoride complexes, which can adopt various coordination geometries, all beryllium fluoride complexes are tetracoordinated, with a Be-F bond length of 1.55 A, and strictly isomorphous to a phosphate group. Our study confirms that fluoride activation of transducin results from a reversible binding of the metal-fluoride complex in the nucleotide site of T alpha, next to the beta phosphate of GDP, as an analogue of the gamma phosphate.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fluoride complexes of aluminium or beryllium act on G-proteins as reversibly bound analogues of the gamma phosphate of GTP. 282 23

The effects of fluoride on ROS phosphodiesterase and G-protein have been studied using membrane-free extracts. When G-protein was present NaF, at millimolar concentrations, stimulated PDE activity however, in a G-protein free extract, cGMP hydrolysis was inhibited by high fluoride concentrations. Fluoride was also found to profoundly inhibit the ability of G-protein to bind a GTP analogue, GTP gamma S, both in the presence and absence of rhodopsin. Aluminium greatly modified these effects of fluoride on PDE and G-protein. The possibility that fluoride activates PDE through its effect on G-protein is discussed.
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PMID:Effects of fluoride on retinal rod outer segment cGMP phosphodiesterase and G-protein. 299 45

Fluoride activation of neutrophils was found to be associated with phosphoinositide turnover, as monitored by the time-dependent accumulation of inositol phosphates. Unlike phosphoinositide turnover induced by the chemotactic peptide, formylmethionylleucylphenylalanine, that induced by fluoride was not inhibited by pretreatment with pertussis toxin. The translocation of protein kinase C activity from the cytosolic to the membrane compartment was also observed in fluoride-stimulated cells. We have proposed that the mode of action of this halide ion involves interaction with a GTP-binding protein which serves as an intermediary unit between the receptors for inflammatory stimuli and the phosphoinositide-specific phosphodiesterase.
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PMID:Use of fluoride ion as a probe for the guanine nucleotide-binding protein involved in the phosphoinositide-dependent neutrophil transduction pathway. 301 68

Fluoride and guanosine 5'-[gamma-thio]triphosphate (GTP gamma S) both activate the hepatocyte membrane polyphosphoinositide phosphodiesterase (PPI-pde) in a concentration-dependent manner. AlCl3 enhances the fluoride effect, supporting the concept that [A1F4]- is the active species. Analysis of the products of inositol lipid hydrolysis demonstrate that phosphatidylinositol bisphosphate is the major lipid to be hydrolysed. Guanosine 5'-[beta-thio]diphosphate (GDP beta S) is an inhibitor of activation of PPI-pde by both fluoride and GTP gamma S. These observations suggest that the guanine nucleotide regulatory protein (termed Gp) bears a structural resemblance to the well-characterized G-proteins of the adenylate cyclase system and the cyclic GMP phosphodiesterase system in phototransduction.
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PMID:Fluoroaluminates mimic guanosine 5'-[gamma-thio]triphosphate in activating the polyphosphoinositide phosphodiesterase of hepatocyte membranes. Role for the guanine nucleotide regulatory protein Gp in signal transduction. 303 62


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