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)

1. A heat-stable modulator protein was partially purified from mouse epidermis. The protein stimulated modulator-depleted cyclic AMP phosphodiesterase from bovine brain in the presence of Ca2+. 2. DEAE-cellulose chromatography of epidermal extracts demonstrated the presence of two main phosphodiesterase activities that hydrolysed both cyclic AMP and cyclic GMP. A minor peak was eluted between 0.1 and 0.3 M-sodium acetate and a major peak was eluted between 0.3 and 0.45 M-sodium acetate. 3. Cyclic AMP phosphodiesterase activity eluted at low salt concentrations was markedly activated by the epidermal modulator protein in the presence of Ca2+. Storage of the enzyme led to a decrease in its sensitivity to the protein modulator. 4. Treatment of mouse skin with the tumour promoter 12-O-tetradecanoylphorbol 13-acetate, which leads to an increase in epidermal cyclic nucleotide phosphodiesterase activity, did not alter the amount of modulator present in soluble epidermal extracts. The tumour promoter decreased the amount of modulator extractable from particulate epidermal preparations with Triton X-100.
...
PMID:Calcium-dependent protein modulator of cyclic nucleotide phosphodiesterases from mouse epidermis. 21 52

When the supernatant fractions from rat brain homogenates were subjected to preparative electrofocusing in a bed of Sephadex G75, several peaks of calmodulin were resolved. A minor peak representing free calmodulin migrated with a pI of 3.8 --4.4. Other peaks of calmodulin activity were observed with isoelectric points at pH 4.8, 5.2, 6.0 and 6.8. The peak of calmodulin activity at 5.2 co-migrated with phosphodiesterase activity which was stimulated 1.8-fold by calcium. A second peak of phosphodiesterase activity detected at pH 8.0 was stimulated 1.2-fold by calcium and occurred in an area where no calmodulin activity could be detected. If isoelectric focusing was done in the presence of 8 M urea only one peak of calmodulin activity was observed with a pI of 4.0--4.4. It is suggested that the multiple peaks of calmodulin resolved by electrofocusing represent calmodulin associated with various proteins which are subject to modulation by calmodulin and calcium.
...
PMID:Calmodulin resolution of multiple peaks of activity by preparative electrofocusing. 22 46

Synaptic vesicles have a Ca(2+)-dependent protein kinase system that may play a role in mediating Ca(2+)-stimulated neurotransmitter release and vesicle function. Calcium's ability to initiate norepinephrine release and protein phosphorylation in synaptic vesicle preparations was shown to be stimulated by the presence of an endogenous heat-stable vesicle protein fraction. The heat stability and characteristics of this endogenous vesicle fraction were similar to those of calmodulin (Ca(2+)-dependent regular protein) isolated from rat and bovine brain. Calmodulin, like endogenous heat-stable vesicle factor, restored calcium's ability to stimulate vesicle neurotransmitter release and protein kinase activity. Calmodulin-like vesicle protein and purified calmodulin were also equally effective in stimulating cyclic nucleotide-dependent phosphodiesterase, further indicating that these two proteins are functionally equivalent. Depolarization-dependent Ca(2+) uptake in intact synaptosomes simultaneously stimulated release of neurotransmitter and phosphorylation of particular synaptic vesicle proteins that were shown in the isolated vesicle preparation to be dependent on Ca(2+) and calmodulin. The results suggest that calcium's effects on neurotransmitter release and presynaptic nerve terminal protein phosphorylation may be mediated by endogenous calmodulin-like proteins.
...
PMID:Stimulation of Ca2+-dependent neurotransmitter release and presynaptic nerve terminal protein phosphorylation by calmodulin and a calmodulin-like protein isolated from synaptic vesicles. 28 24

Pharmacodynamic characteristics of pentoxyfylline (BL 191) related to insulin secretion by the isolated perfused rat pancreas are studied. The results obtained show that: 1) BL 191 (5 mM) is capable of stimulating insulin secretion, even in the presence of another stimulator; 2) BL 191 increases both phases of the secretion produced by constant arginine 20 mM/glucose 5 mM perfusion; 3) BL 191 significantly increases and turns biphasic the monophasic insulin secretion pattern produced by 1 microgram/ml glibenclamide; 4) the effects mentioned in points 2) and 3) are inhibited if the phosphodiesterase activator imidazole (300 mg/100 ml) is present in the perfusion medium; 5) the phosphodiesterase inhibitor theophylline has the same effects as BL 191, except for its inability to stimulate insulin release in the absence of another stimulator; 6) somatostatin (100 ng/ml) significantly inhibits insulin secretion produced by arginine/glucose or glibenclamide, as well as by arginine, glucose plus theophylline or BL 191, and by glibenclamide plus theophylline or BL 191, in both cases the inhibitory effect of somatostatin is reduced by the presence of BL 191 or theophylline.
...
PMID:The influence of pentoxyfylline [1-(5-oxohexyl-) 3,7-dimethylxanthine] (BL 191) on the insulin secretion induced by glibenclamide and by arginine/glucose in the perfused pancreas. 41 15

Calmodulin, a heat-stable Ca2+-binding protein (Mr = 16,700) found in all eukaryotes, is a multifunctional modulator, mediating many of the effects of Ca2+ in cellular functions. The protein was derivatized with 1-fluoro-2,4-dinitrobenzene (DNB) to give 3 mol of DNB/mol of calmodulin (DNB3-calmodulin). The dinitrophenylated protein was almost as active as native calmodulin in stimulating bovine brain Ca2+-dependent phosphodiesterase. Incorporation of the dinitrophenyl groups renders calmodulin highly antigenic in the rabbit; native calmodulin is a weak antigen. Rabbits immunized with DNB3-calmodulin produced specific antibody against both DNB3-calmodulin and calmodulin. Using the immunized serum, a radioimmunoassay was developed for calmodulin, the sensitivity for DNB3-calmodulin and calmodulin being approximately 0.2 and 2 pmol, respectively. Although the sensitivity of the radioimmunoassay for calmodulin is comparable to the enzyme assay of calmodulin with Ca2+-dependent phosphodiesterase, the radioimmunoassay affords the detection of calmodulin on the basis of antigenic determinants, and thus measures calmodulin in terms of polypeptide structure instead of its ability to stimulate an enzyme. Further, the accuracy of the radioimmunoassay is not affected by the presence of a heat-labile inhibitor protein, which affects the enzyme assay to give an apparent underestimation.
...
PMID:Calmodulin. Production of an antibody in rabbit and development of a radioimmunoassay. 44 35

The calmodulin contents of rabbit brain, lung, kidney and liver, of bovine aorta and uterus, and of chicken gizzard have been determined. 2. The calmodulin in all of these tissues has been shown to be present in the form of very stable complexes with several other proteins. 3. A calmodulin-binding protein of mol.wt. 22 000 has been purified in high yield from bovine brain. It has been shown to interact with calmodulin and rabbit skeletal-muscle troponin C in a Ca2+-dependent manner. 4. The 22 000-mol.wt. protein inhibits the activation of bovine brain phosphodiesterase by calmodulin, but has very little affect on the activation of myosin light-chain kinase. 5. Calmodulin-binding proteins of mol.wts. 140000, 77000 and 61000 have also been partially purified from rabbit brain by affinity chromatography and have been shown to interact in a Ca2+-dependent manner with calmodulin. 6. The apparent molecular weights of the calmodulin-calmodulin-binding protein complexes, determined by gel filtration in the presence of 6M-urea, have been shown to be similar for most of the mammalian tissues examined. 7. By using 125I-labelled calmodulin, similar complexes have been demonstrated in rabbit skeletal muscle, although they are present at much lower concentrations.
...
PMID:Calmodulin-binding proteins from brain and other tissues. 53 97

Myosin light chain kinase which phosphorylates g2 light chain of skeletal muscle myosin requires an activator for the activity (Yazawa, M., and Yagi, K (1977) J. Biochem. (Tokyo) 82, 287-289). This activator has now been identified as the modulator protein known to be a Ca2+-dependent regulator for phosphodiesterase, adenylate cyclase, and ATPases. The identification is based on the quantitative cross-reactivity of muscle activator protein and brain modulator protein in activating myosin light chain kinase and brain phosphodiesterase and identical properties of both proteins in regard to sensitivities to Ca2+, UV absorption spectra, UV absorption difference spectra with or without Ca2+, and mobilities upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In the presence of modulator protein, the activity of myosin light chain kinase was reversibly controlled by the physiological concentration of Ca2+. We suggest that two Ca2+-receptive proteins, i.e. modulator protein and troponin-C, may play roles in the contraction-relaxation cycle of skeletal muscle.
...
PMID:Identification of an activator protein for myosin light chain kinase as the Ca2+-dependent modulator protein. 62 40

[Met5]-Enkephalin (ME) secretion and the expression of proenkephalin A (proENK) mRNA were studied following long-term exposure of bovine adrenal medullary chromaffin (BAMC) cells to pertussis toxin. Treatment with pertussis toxin for 24 h increased the secretion of ME in a concentration- and time-dependent manner. The magnitude of ME secretion continued to increase with time in the presence of pertussis toxin. The intracellular concentration of ME in the pertussis toxin-treated group was not significantly different from controls, suggesting that elevated levels of ME secretion result from increased biosynthesis of ME rather than from release of stored ME. Prolonged (24 h) stimulation of BAMC cells with pertussis toxin also increased proENK gene expression. Pretreatment with nimodipine (a calcium channel blocker) and calmidazolium (a calmodulin antagonist) inhibited both the secretion of ME and the increase in proENK mRNA levels induced by pertussis toxin, while the intracellular calcium antagonist dantrolene and the protein kinase C inhibitors sphingosine and H7 [1-(5-isoquinolinylsulfonyl)-2-methylpiperazine] were ineffective in blocking pertussis toxin-induced responses. Forskolin (an adenyl cyclase activator) and isobutyl methyl xanthine (a phosphodiesterase inhibitor) increased both ME secretion and proENK mRNA levels; pertussis toxin synergistically increased the secretion of ME with these cyclic AMP-elevating agents but had only an additive effect with these agents on the level of proENK mRNA. Our results suggest that a pertussis toxin-sensitive G protein may tonically regulate the secretion of ME as well as the level of proENK mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Pertussis toxin stimulates the secretion of [Met5]-enkephalin and the expression of proenkephalin A mRNA in bovine adrenal medullary chromaffin cells. 128 24

In the preceding paper (Kawai, H. et al. (1992) Biochim. Biophys. Acta 1133, 172-178), we reported that in mastocytoma P-815 cells dexamethasone and 12-O-tetradecanoylphorbol-13-acetate (TPA) synergistically enhanced the de novo synthesis of L-histidine decarboxylase (HDC). Here we found that Ca2+ acted synergistically with cAMP in the induction of HDC mRNA and HDC activity in mastocytoma P-815 cells, and that the mechanism underlying the enzyme induction by Ca2+ plus cAMP was distinguishable from that by dexamethasone plus TPA. Ca2+ ionophore A23187, itself having no significant activity, markedly enhanced the induction of HDC activity by N6,O2'-dibutyryl cAMP (db cAMP) or cAMP-inducible prostaglandins such as PGE1, PGE2 and PGI2 in the presence of the phosphodiesterase inhibitor, Ro201724. However, A23187 had little effect on increases in HDC activity induced by other known stimulants, such as TPA, dexamethasone and sodium butyrate. These results suggest that A23187 has a specific effect on the induction of HDC activity due to an increased level of cAMP. The finding that both A23187 and cAMP enhanced HDC activity suggests that both Ca2+/calmodulin and cyclic nucleotide dependent protein kinase play essential roles in the process of enhancement of HDC activity. To examine this possibility, we studied the effects of W-7, an inhibitor of calmodulin, removal of extracellular Ca2+, and H-8, an inhibitor of cAMP-dependent protein kinase, on the enhancing activity of A23187 plus db cAMP. The enhancement of HDC activity by A23187 plus db cAMP was inhibited by W-7, removal of extracellular Ca2+, and H-8. The increase in HDC activity was due to the de novo synthesis of the enzyme, since it was suppressed by the addition of cycloheximide or actinomycin D, and was well correlated with the marked accumulation of a 2.7 kilobase HDC mRNA. Furthermore, the mechanism underlying the induction of HDC by db cAMP plus A23187 is distinguishable from that in the case of dexamethasone plus TPA, since preexposure to dexamethasone plus TPA for 12 h, for a plateau level to be reached, did not affect the subsequent increase in HDC activity due to db cAMP plus A23187.
...
PMID:Synergistic effects of cyclic AMP and Ca2+ ionophore A23187 on de novo synthesis of histidine decarboxylase in mastocytoma P-815 cells. 131 51

Endogenous calmodulin (CaM) in the EGTA-washed cerebral-cortical synaptosomal membrane (SM) preparation was estimated below 3 micrograms/ml protein by the semiquantitative immunoblot analysis (Natsukari, N., Ohta, H. and Fujita, M. (1989) J. Immunol. Methods 125, 159-166). Membrane-bound CaM was immunoelectron-microscopically demonstrated in EGTA-washed, non-treated (control), and Ca(2+)-treated cerebral-cortical synaptosomal membranes (SM) as well as for the SM enriched with added CaM. The density of CaM increased in the above order. CaM-dependent adenylate cyclase and CaM-dependent protein kinase II (CaM-kinase II) activities were restored, whereas the phosphodiesterase (PDE) activity was not affected by exogenous CaM over all the Ca2+ concentrations tested. Adenylate cyclase at pCa 6.2 was synergistically activated either by GTP and CaM or by CaM and beta-adrenergic agonist, (+/-)-isoproterenol, reflecting the intactness of signal transduction pathway in the SM. Also demonstrated were the presence of protein kinase A, CaM-kinase II, and their endogenous substrates in the SM. Based on 32P-autoradiography and 125I-CaM overlay data certain CaM-binding proteins such as CaM-kinase II and synapsin I were identified on SDS-PAGE. Ca(2+)-dependent and -independent CaMBPs were distinguished by 125I-CaM gel overlay with and without Ca2+. The former had bigger molecular size (greater than or equal to 49 kDa) than the latter (less than or equal to 34 kDa). Yield of Ca(2+)-dependent CaMBPs was not affected by Ca2+ concentration during preparation of the SM while that of Ca(2+)-independent CaMBPs was reduced by exposure to 100 microM Ca2+. In contrast with the CaMBPs of brain SM, those of enterocyte and eyrthrocyte plasma membranes especially, microvillous membrane of the enterocyte, showed quite distinct CaMBP profiles. The present findings suggested that the EGTA-washed SM preparation made a useful system for studying the role of CaM in the brain SM.
...
PMID:Characterization of EGTA-washed synaptosomal membrane with emphasis on its calmodulin-binding proteins. Demonstration of possible reconstitution with added calcium/calmodulin. 131 53


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

---