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

---

Query: EC:3.1.4.1 (phosphodiesterase)
18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The new phosphodiesterase-III inhibitor (PDI) enoximone is a non-catecholamine, non-glycoside cardiotonic agent with concomitant vasodilating properties. It has proved beneficial in patients with severe chronic heart failure. The influence of enoximone i.v. on hemodynamics was investigated during cardiac surgery under various conditions. METHODS. A randomized series of 60 patients undergoing elective aorto-coronary bypass grafting were studied. The hemodynamic effects of 0.5 mg/kg enoximone given i.v. as a bolus (30 s) were investigated before anesthesia (n = 10), during anesthesia (n = 10), and during extracorporeal circulation (ECC, n = 10) and compared with those observed in corresponding control groups (n = 10 in each control) of patients who had received saline solution as placebo. Anesthesia was maintained with weight-dependent dosages of fentanyl, midazolam and pancuronium bromide. All patients were invasively monitored by means of a pulmonary artery catheter. Additionally, left ventricular pressure (LVP), left ventricular end-diastolic pressure (LVEDP) and dp/dtmax were measured before the initiation of ECC. During ECC direct vascular effects were investigated with measurement of perfusion pressure and the volume of the oxygenator. RESULTS. Before the induction of anesthesia no significant change in MAP and HR could be observed, whereas CI increased (+20%) and TSR decreased (-24%) significantly. During anesthesia, the injection of enoximone was followed by a significant decrease in MAP only in the 1st min (-17%); baseline level was reached again after 6 min; and HR was slightly increased (+8%). TSR (-31%) and LVEDP (-38%) decreased, whereas CI (+17%) and dp/dtmax (+45%) were increased significantly. During ECC perfusion pressure (-37%) and the volume of the oxygenator (-17%) were significantly decreased, demonstrating direct vasodilating effects on both the arteries and the vein. CONCLUSION. Arterial and venous vasodilation with an increase in myocardial performance (dp/dtmax) resulting in an increase in CI were the predominant hemodynamic effects of enoximone i.v. No arrhythmogenic effects or interactions with the anesthetics used were observed in this study.
...
PMID:[Hemodynamic effects of the new phosphodiesterase inhibitor enoximone in heart surgery patients]. 252 51

The three stereoisomers of P1,P4-bis(5'-adenosyl)-1,4-dithiotetraphosphate have been synthesized and their 31P NMR spectra investigated. The effect of temperature on the circular dichroic spectrum of the (Sp,Sp)-stereoisomer shows that unstacking of the molecule occurs as the temperature is raised. Treatment of the (Sp,Sp)-stereoisomer with cyanogen bromide in [18O]water leads to substitution of sulfur by 18O with predominant retention of configuration at P1 and P4. (Sp,Sp)-P1,P4-Bis(5'-adenosyl)-1[thio-18O2],4[thio-18O2]tetraphosphate was synthesized and on treatment with cyanogen bromide in [17O]water gave (Rp,Rp)-P1,P4-bis(5'-adenosyl)-1[17O,18O2],4[17O,18O2]tetraphosphate. Hydrolysis by unsymmetrical Ap4A phosphodiesterase from lupin seeds gave (Rp)-5'-[16O,17O,18O]AMP. The reaction therefore proceeds with inversion of configuration at phosphorus, indicating that the enzyme-catalyzed displacement by water occurs by a direct "in-line" mechanism.
...
PMID:Synthesis of (Rp,Rp)-P1,P4-Bis(5'-adenosyl)-1[17O,18O2],4[17O,18O2] tetraphosphate from (Sp,Sp)-P1,P4-Bis(5'-adenosyl)-1[thio-18O2], 4[thio-18O2]tetraphosphate with retention at phosphorus and the stereochemical course of hydrolysis by the unsymmetrical Ap4A phosphodiesterase from lupin seeds. 253 99

The effect of intracellular perfusion with cyclic GMP (cGMP) on Ca current (Ica) was investigated in Cs-loaded isolated cells from guinea pig ventricle using the whole-cell patch-clamp technique and a perfused patch pipette. cGMP (5 microM) strongly reduced Ica which had been elevated by intracellular perfusion with 50 microM of either cyclic AMP (cAMP) or its hydrolysis-resistant analog 8-Bromo-cAMP. In addition, cGMP prevented the stimulation of Ica by IBMX, a phosphodiesterase inhibitor. The membrane permeant cGMP analog 8-Bromo-cGMP (100 microM), when applied outside the cell, also antagonized the stimulatory effect of IBMX on Ica. It is concluded that cGMP inhibits Ica in guinea pig ventricular cells by a mechanism different from the activation of a cGMP-stimulated phosphodiesterase recently found in frog ventricular cells.
...
PMID:Cyclic GMP regulates the Ca-channel current in guinea pig ventricular myocytes. 254 86

cGMP-stimulated phosphodiesterase (PDE) has been directly photolabeled with [32P]cGMP using UV light. Sequence analysis of peptide fragments obtained from partial proteolysis or cyanogen bromide cleavage indicate that two different domains are labeled. One site, on a Mr = 36,000 chymotryptic fragment located near the COOH terminus, has characteristics consistent with it being close to or part of the catalytic site of the enzyme. This peptide contains a region of sequence that is highly conserved in all mammalian cyclic nucleotide PDEs and has been postulated to contain the catalytic domain of the enzyme. The other site, on a Mr = 28,000 cyanogen bromide cleavage fragment located near the middle of the molecule, probably makes up part of the allosteric site of the molecule. Labeling of the enzyme is concentration dependent and Scatchard analysis of labeling yields a biphasic plot with apparent half labeling concentrations of about 1 and 30 microM consistent with two types of sites being labeled. Limited proteolysis of the PDE by chymotrypsin yields five prominent fragments that separate by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) at Mr = 60,000, 57,000, 36,000, 21,000, and 17,000. Both the Mr = 60,000 and 57,000 apparently have blocked NH2 termini suggesting that the Mr = 57,000 fragment is a subfragment of the Mr = 60,000 fragment. Primary sequence analysis indicates that both the Mr = 21,000 and 17,000 fragments are subfragments of the Mr = 36,000 fragment. Autoradiographs of photolabeled then partially proteolyzed enzyme show labeled bands at Mr = 60,000, 57,000, and 36,000. Addition of 5 microM cAMP prior to photolabeling eliminates photolabeling of the Mr = 36,000 fragment but not the Mr = 60,000 or 57,000 fragments. The labeled site not blocked by cAMP is also contained in a Mr = 28,000 cyanogen bromide fragment of the enzyme that does not overlap with the Mr = 36,000 proteolytic fragment. Limited chymotryptic proteolysis also increases basal activity and eliminates cGMP stimulation of cAMP hydrolysis. The chymotryptic fragments can be separated by either ion exchange high performance liquid chromatography (HPLC) or solid-phase monoclonal antibody treatment. A solid-phase monoclonal antibody against the cGMP-stimulated PDE removes the Mr = 60,000 and 57,000 labeled fragments and any intact, unproteolyzed protein but does not remove the Mr = 36,000 fragment or the majority of activity. Ion exchange HPLC separates the fragments into three peaks (I, II, and III). Peaks I and II contain activity of approximately 40 and 100 units/mg, respectively. Peak II is the undigested or slightly nicked native enzyme.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Direct photolabeling of the cGMP-stimulated cyclic nucleotide phosphodiesterase. 254 73

The thyroid tissue is innervated by cholinergic and VIPergic nerves. The present study investigated the possible interactions of cholinergic agents with VIP-induced cAMP accumulation and thyroid hormone release in vitro. Carbamylcholine (Cch), acting through the muscarinic receptor increases cellular cGMP content in cultured human thyroid cells incubated with a phosphodiesterase inhibitor. Cch (10 microM) inhibits cellular cAMP accumulation and thyroxine (T4) release induced by vasoactive intestinal peptide (VIP), with or without a phosphodiesterase inhibitor. Cch (10 microM) inhibits 8-bromo-cAMP-induced T4 release from human thyroid slices. 8-Bromo-cGMP inhibits VIP-induced T4 release from human thyroid slices, only in cells incubated without the phosphodiesterase inhibitor. The results indicate that interactions between VIPergic and cholinergic receptors may be of importance in human thyroid cell.
...
PMID:Interaction of VIPergic and cholinergic receptors in human thyroid cell. 282 44

Differentiation in the mouse neuroblastoma cells is induced by cAMP and is characterized by neurite extension and increased acetylcholinesterase, cAMP-phosphodiesterase, and RI cAMP-binding activities. To gain a better understanding of the regulation of expression and the possible function of the RI cAMP-binding protein in neuroblastoma cell differentiation, we evaluate the specificity of action of cAMP analogues and agents that increased intracellular cAMP concentration in the induction of the 47,000-dalton RI protein. The amount of RI in cell extracts was quantitated by the photoactivated incorporation of 8-N3-[32P]cAMP into the 47,000-dalton RI and by ELISA and Western blot techniques. Our results showed that dibutyryl cAMP, forskolin, prostaglandin E1, 3-isobutyl-1-methyl xanthine, and papavarine gave a 2- to 4-fold increase in the RI cAMP-binding protein coincident with the expression of various morphological and biochemical differentiation phenotypes in the mouse neuroblastoma cells. However, the effects of 8-bromo-cAMP were different. 8-Bromo-cAMP effectively promoted neurite extension and increased acetylcholinesterase and cAMP-phosphodiesterase activities; however, there was no concomitant increase in the RI cAMP-binding protein. The result raises interesting questions concerning the coupling of expression of the various differentiation phenotypes in the mouse neuroblastoma cells.
...
PMID:Specificity of the action of cAMP agonists in the induction of RI cAMP-binding protein in mouse neuroblastoma cells. 283 19

SIE AP mass spectra of tryptic peptides from the cyclo-GMP phosphodiesterase gamma-subunit and of chymotryptic peptides from the cyanogen bromide fragments of the same subunit exhibit MH+ ions for all theoretically possible smaller peptides. These facts show that SIE AP mass spectrometry can be successfully applied to peptide mapping using 1-2 nmoles of the compound.
...
PMID:[Mass-spectrometry with ion extraction from solution at atmospheric pressure for peptide mapping]. 283 31

Phosphatases and phosphodiesterases that hydrolyse polyphosphoinositides are described in both membrane and cytosol fractions of human, pig, rat, rabbit, and sheep erythrocytes using exogenous substrates. With suitably optimized assay conditions, Ca2+-dependent phosphatidylinositol bisphosphate (PIP2) phosphodiesterase activity was found in the hemoglobin-free cytosol fraction, as well as the membrane. Membrane activity is completely dependent upon Triton X-100 and salt and inhibited by cetyltrimethylammonium bromide (CTAB), while the soluble activity requires CTAB and is inhibited by Triton. A low Ca2+-dependent PIP2 phosphatase activity, not present in other tissues, was also detected. The cation-independent phosphatidylinositol phosphate (PIP) phosphatase is localized in the membrane in most species, while the diesterase and the PIP2 phosphatases (both Mg2+ and Ca2+ dependent) are localized in the cytosol. Rat and rabbit erythrocytes are atypical in having a substantial proportion of their Mg2+-dependent PIP2 phosphatase activities in the membrane. All activities are lowest in sheep erythrocytes, except the PIP phosphatase, most of which is soluble in this species. Ca2+-dependent PIP2 phosphatase activity is not correlated with the activity or subcellular distribution of any of the other hydrolases and seems to be a separate enzyme. All the phosphoinositide hydrolase activities, particularly the diesterase, are orders of magnitude lower in erythrocytes than in other tissues. Both soluble and membrane diesterase activities are lost as erythrocytes age. Soluble polyphosphoinositide diesterase does not seem to be active with membrane-bound substrate, since pig and sheep erythrocytes that have negligible membrane activity do not respond to Ca2+ loading, yet have substantial diesterase activity in the cytosol. This supports the view that the diesterase is not physiologically functional in normal erythrocytes.
...
PMID:Soluble and membrane-bound polyphosphoinositide phosphohydrolases in mammalian erythrocytes. 283 56

The effects of follicle-stimulating hormone (FSH) and cyclic guanosine 3',5'-monophosphate (cGMP) on spontaneous oocyte maturation and cyclic adenosine 3',5'-cumulus-monophosphate phosphodiesterase activity (cAMP-PDE) were evaluated by using cumulus-oocyte complexes (COCs) from proestrous hamsters. After a 2-h incubation period, FSH (10 micrograms/ml and 1 microgram/ml) reduced the percentage of maturing oocytes compared with controls. This inhibition was partially overcome when cGMP-elevating agents (8-Bromo-cGMP, atrial natriuretic factor or sodium nitroprusside) were included with FSH. After a 3-h period, incubation with FSH and cGMP-elevating agents alone increased the maturation rate above that of the controls. The accelerating effects of cGMP on the maturation rate appear to be caused by its capacity to lower cAMP levels. Combining FSH (1 microgram/ml) with sodium nitroprusside reduced cAMP levels in COCs (not oocytes) compared with groups exposed to FSH alone. FSH increased cGMP levels in COCs in a dose- and time-dependent manner. Both FSH and cGMP-elevating agents produced a dose-dependent increased cAMP-PDE activity in COCs (not oocytes) following a 2-h incubation period. Together, these results suggest that, in vivo, FSH stimulates a rise in both cAMP and cGMP in COCs. While the increase in cAMP may be the initial meiotic trigger, cGMP may serve to subsequently lower cAMP by activating cAMP-PDE and thus permit the maturational process to continue.
...
PMID:The effects of follicle-stimulating hormone and cyclic guanosine 3',5'-monophosphate on cyclic adenosine 3',5'-monophosphate-phosphodiesterase and resumption of meiosis in hamster cumulus-oocyte complexes. 285 23

Some smooth muscle relaxant drugs with an unknown mechanism of action have been tested for their interaction with calmodulin and with calmodulin-induced cyclic nucleotide phosphodiesterase (PDE) activity. The affinity of these drugs for calmodulin does not parallel their inhibitory effect on the calmodulin activation of PDE. The lack of parallelism could be due to a binding of the drugs to different sites on calmodulin; furthermore a binding of papaverine, octylonium bromide and felodipine to PDE molecule might also be considered to explain their inhibitory effect on PDE basal activity. The myolytic effect of octylonium bromide and pinaverium bromide may be due to their interaction with calmodulin-dependent systems.
...
PMID:Interaction of smooth muscle relaxant drugs with calmodulin and cyclic nucleotide phosphodiesterase. 298 1


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---