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)

Correlative electrophysiological and biochemical techniques were used to study hippocampal post-tetanic potentiation in acutely prepared rabbits following stimulation of the medial septal region and contralateral hippocampal field CA3. The results indicate that calcium ions, guanosine-3':5'-monophosphate, and phosphodiesterase inhibitors selectively enhanced the duration of post-tetanic potentiation. Potassium ions selectively enhanced tetanic potentiation. Adenosine-3':5'-cyclic monophosphate suppressed both tetanic and post-tetanic potentiation. The electrophysiological findings were supported by biochemical observations that guanosine-3':5'-monophosphate levels show marked increases following tetanic stimulation of either the medial septal region or contralateral hippocampal field CA3 pathways. The data suggest that a calcium-dependent process in the presence of a guanosine-3':5'-monophosphate mechanism promotes periods of hippocampal pyramidal cell hyperexcitability. The mechanism by which the cyclic nucleotide alters potentiation does not appear to be coupled to a single receptor variety.
...
PMID:Evidence for a cyclic GMP mechanism in the mediation of hippocampal post-tetanic potentiation. 631 Jan 37

Adenosine, 2-chloroadenosine, adenosine triphosphate (ATP) and adenosine tetraphosphate induced concentration-dependent relaxation of rat caecum. Caffeine as well as theophylline, at concentrations (25-100 microM) lower than that known to produce significant phosphodiesterase inhibition, shifted the concentration-response curve for adenosine to the right in a parallel fashion without diminishing the maximal response. The pA2 values for caffeine and theophylline against adenosine were found to be 4.6 +/- 0.26 (slope = 0.97 +/- 0.05) and 4.9 +/- 0.28 (slope = 0.98 +/- 0.07), respectively. Though the relaxant effect of adenosine tetraphosphate was blocked in a non-competitive manner by quinidine (5 microM) and phenoxybenzamine (25 microM), theophylline or caffeine (50 microM) failed to block this response. Similarly, quinidine also blocked the relaxant effect of ATP in a non-competitive manner. Besides, the relaxant effect due to adensine was rapid in onset as compared to a slow relaxant effect of ATP. These observations suggest the presence of P1- and P2-purinoceptors in the caecum. The activation of these receptors by adenosine and ATP, respectively, leads to relaxation of the tissue.
...
PMID:Evidence for the presence of P1- and P2-purinoceptors in rat caecum. 631 21

Adenosine by interaction with discrete extracellular recognition sites can modulate cyclic AMP formation and cell firing in the mammalian CNS. The effects of adenosine on cyclic AMP formation are mediated through two extracellular recognition sites: a high affinity (Kd = 10(-9) M) site designated A-1, activation of which results in an inhibition of adenylate cyclase activity and a lower affinity site (Kd = 10(-6) M) designated A-2, activation of which stimulates adenylate cyclase activity. Stable radiolabeled analogs of adenosine have been used to label A-1 receptors in mammalian brain. Adenosine and its stable analogs are potent inhibitors of neurotransmitter release. In addition to being phosphodiesterase inhibitors, the alkylxanthines are also adenosine antagonists, stimulating neurotransmitter release and increasing cell firing by antagonism of the effects of endogenous adenosine. These effects have been attributed to the presence of an inhibitory purinergic tone. Adenosine and related purines have been implicated in the mode of action of several centrally active drugs including anxiolytics, antidepressants and analgesics. Future progress in understanding the potential physiological role of adenosine in the mammalian CNS will depend on the availability of more potent and specific adenosine antagonists, ligands specific for the A-2 receptor, and a better understanding of the factors that regulate adenosine availability.
...
PMID:Adenosine receptors in the mammalian central nervous system. 632 Feb 95

Adenosine, 2-chloroadenosine and prostaglandin E1 which are known to increase cyclic AMP in neuroblastoma cells potentiated the acetylcholine-induced muscarinic hyperpolarization of the cells without changing the resting membrane potential. The potentiation caused by 2-chloroadenosine was further augmented by Ro 20-1724, a phosphodiesterase inhibitor. A direct intracellular pressure application of cyclic AMP potentiated the muscarinic hyperpolarization without changing the resting membrane potential. Morphine which inhibits adenylate cyclase antagonized 2-chloroadenosine-induced potentiation of the muscarinic hyperpolarization. These results suggest that changes in cyclic AMP level modulate the muscarinic response of neuroblastoma cells.
...
PMID:Cyclic AMP-mediated potentiation of muscarinic hyperpolarization in neuroblastoma cells. 632 Sep 77

The synthesis of prostacyclin by human venous tissue in vitro and the effects of aspirin and dipyridamole thereon were investigated. Dipyridamole significantly stimulated prostacyclin production in a concentration range of 25 to 100 microM. Dipyridamole significantly attenuated the inhibitory effect of 0.1 mM aspirin in a concentration range of 12.5 to 100 microM. Isobutylmethylxanthine 0.1 mM, an unrelated inhibitor of phosphodiesterase, had similar effects to dipyridamole. Cyclic AMP 3.0 mM had an inhibitory effect on prostacyclin synthesis in the presence of dipyridamole. Adenosine 0.1 mM and nitrobenzylthioguanosine 0.1 mM, an inhibitor of adenosine uptake, did not significantly influence prostacyclin synthesis in this system. We conclude that the stimulation of prostacyclin synthesis by dipyridamole is unrelated to the ability of this drug to block the high-affinity uptake of adenosine by endothelial cells and that the effect may also be independent of changes in the concentration of cAMP induced by the drug.
...
PMID:A study of the stimulation of human venous prostacyclin synthesis by dipyridamole. 675 83

Whole-cell patch-clamp recordings from Vicia faba mesophyll protoplasts reveal that outward K+ current is increased in a dose-dependent fashion by intracellular application of cAMP. The enhancement of the outward current by cAMP is specific and it cannot be mimicked by a series of nucleotides that includes AMP, cGMP, and GMP. The enhancement is evoked by micromolar concentrations of cAMP in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine. PKI or Walsh inhibitor, a specific peptide inhibitor of cAMP-dependent protein kinase (PKA), inhibits the outward K+ current. Adenosine 3',5'-phosphothioate, a competitive inhibitor of PKA, has a similar effect. Conversely, the catalytic subunit of PKA (cAMP independent) from bovine brain enhances the magnitude of the outward K+ current in the absence of added cAMP. Our results indicate that cAMP modulates K+ channel activity in mesophyll cells and suggest that this modulation occurs through a cAMP-regulated protein kinase.
...
PMID:Cyclic AMP stimulates K+ channel activity in mesophyll cells of Vicia faba L. 752 28

On removal from the animal, molluscan hemocytes change from an aggregation-incompetent state to one in which they aggregate and stick avidly to foreign surfaces. Aggregation and substratum adhesion behaviors of Mytilus californianus (California mussel) hemocytes are inhibited reversibly and non-lethally by caffeine. We investigated the mechanistic basis of this inhibition by means of assays that determined the abilities of several compounds to compete or synergize with caffeine in achieving its effect. Adenosine and the adenosine receptor agonists 2-chloro-adenosine or 5'-N-ethylcarboxamido-adenosine reversed caffeine inhibition. In contrast, isobutyl-methyl-xanthine (both an adenosine receptor antagonist and an inhibitor of phosphodiesterase) and the adenosine receptor antagonists cyclo-hexyladenosine and R-N6-phenyl-isopropyladenosine synergized with caffeine to inhibit hemocyte adhesion. Caffeine treatment reduced intracellular cAMP. Alterations in cAMP concentrations in response to caffeine with or without adenosine and adenosine analogues reflected alterations in adhesion behavior in the same drugs. R-N6-phenyl-isopropyladenosine plus caffeine yielded intracellular cAMP levels lower than those in cells treated with caffeine alone. However, both cAMP level and hemocyte adhesion increased when adenosine or 5'-N-ethylcarboxamido-adenosine replaced R-N6-phenyl-isopropyladenosine. This mollusc's hemocytes appear to express adenosine receptors that modulate phagocyte behavioral responses by altering second messenger transduction.
...
PMID:Hemocyte adhesion in the California mussel (Mytilus californianus): regulation by adenosine. 766 6

Porcine brain-derived microvascular endothelial cells (BMEC) express the mRNA of the polypeptide mitogen vascular permeability factor/vascular endothelial growth factor (VPF/VEGF). The VEGF mRNA expression in BMEC could be upregulated 2.5 fold after 6 h of treatment with 5 microM adenosine and adenosine agonists. Adenosine A1 and A2 receptor antagonists completely abolished the upregulation of the VEGF mRNA caused by adenosine. Agents like forskolin and cAMP phosphodiesterase inhibitors which are known to increase the cAMP level decreased the VEGF mRNA expression slightly whereas agents like phorbolester which activate the proteinkinase C (PKC) pathway enhanced the VEGF mRNA expression 3.2 fold. The specific inhibitor of the PKC bisindolymaleimide (BIM) abolished the upregulation of the VEGF mRNA by adenosine completely. The BMEC conditioned medium stimulated the proliferation of BMEC itself and Western blot analysis of the BMEC conditioned medium using a polyclonal antibody to human VEGF showed one band at 18 kDa which was slightly upregulated after treatment with adenosine. Results suggest that the effect of adenosine on the VEGF mRNA expression is mediated via the A1 receptor and that an activation of the PKC may be involved in the observed effects of adenosine on the VEGF mRNA expression. VEGF produced by BMEC and which is inducible by adenosine may function via the autocrine pathway and may be involved in repair reactions of brain blood vessels and/or the maintenance of these cells.
...
PMID:Expression of vascular permeability factor/vascular endothelial growth factor in pig cerebral microvascular endothelial cells and its upregulation by adenosine. 770 68

1. Adenosine is an endogenous neuroprotective agent; stimulation of A1 receptors decreases excitatory amino acid neurotransmission and stimulation of A2 receptors inhibits platelet and neutrophil activation and promotes vasodilation. 2. Post-ischemic administration of propentofylline (HWA 285) reduces neuronal damage in gerbils and improves glucose metabolism in all regions of brain in acute stroke patients. 3. Propentofylline inhibits the transport of adenosine into cultured cells and increases extracellular adenosine concentrations in ischemic brain. Thus, enhanced stimulation of adenosine receptors may account for some of the neuroprotective effects of this compound. 4. Propentofylline inhibits free radical production by cultivated microglia cells, stimulates nerve growth factor production and inhibits cAMP-phosphodiesterase activity. These effects may also be important for neuroprotection.
...
PMID:Propentofylline: a nucleoside transport inhibitor with neuroprotective effects in cerebral ischemia. 787 26

Adenosine diphosphate (ADP)-ribose 1",2"-cyclic phosphate (Appr > p) is produced as a result of transfer RNA (tRNA) splicing in the yeast Saccharomyces cerevisiae and probably in other eukaryotes. Endonucleolytic cleavage and ligation result in a mature length tRNA with a 2'-phosphate at the splice junction. This 2'-phosphate is transferred to NAD to produce Appr > p. Metabolism of Appr > p requires hydrolysis of the 1",2"-cyclic phosphate linkage. We show here that yeast has a unique cyclic phosphodiesterase that can hydrolyze Appr > p, ribose 1,2-cyclic phosphate, and ribose 1,3-cyclic phosphate to the corresponding ribose 1-phosphate derivatives. The cyclic phosphodiesterase is highly specific for Appr > p; there is 20-fold less activity on ribose 1,3-cyclic phosphate and no detectable activity on nucleoside 2',3'-cyclic phosphates. A similar cyclic phosphodiesterase is present in wheat germ. The wheat germ cyclic phosphodiesterase activity co-chromatographs with a 2',3'-cyclic nucleotide 3'-phosphodiesterase that was previously identified and purified. The purified wheat germ enzyme has a distinct preference for Appr > p and ribose cyclic phosphate compared to guanosine 2',3'-cyclic phosphate and shares other biochemical characteristics with the yeast enzyme.
...
PMID:tRNA splicing in yeast and wheat germ. A cyclic phosphodiesterase implicated in the metabolism of ADP-ribose 1",2"-cyclic phosphate. 792 75


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

---