Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effect of Etafenone on the Cardisotimulatory (1) In the isolated guinea-pig heart (Langedorff), 2'-[2-(diethylamino)-ethoxy]-3 -phenyl-propioheonoe HCI (etafenone, Baxacor) produced a parital and non-competitive inhibition of the stiumulant actions of isoprenaline on glycogen phosphorylase, rate and amplitude of contraction, but did not reduce the increase in coronary flow. (2) In isolated cirular strips from bovine coronary arteries, etafeonoe reduced tension (ED 50 = 2.8 x 10-5M), and increased the relaxing effect of isoprenaline. (3) Etafeonoe inhbitied the acitivty of phosphodiesterase in vitro; the Ki value with the enzyme frombovine coronary arteries was 9.2x10-4M, which was 160-fold higher than the Ki for papaverine.(4) The results suggest that etafenone probably affects the myocardial as well as the coronary smoth muscle cell by a direct inhibitory effect on Caiinflux, which could accountfor the depressant effect and the non-competitive antagonism aginst isoprenaline in the heartas well as the relaxing action on coronary smooth muscle. The inhibitory effect on phospodiesterase is likely to contribute to the relaxing action of etafenone by accumulation ofcyclic AMP.
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PMID:Modification of the cardiostimulatory and coronary dilator effect of isopreenaline caused by etafenone. 23 42

The effect of mepacrine (DL-quinacrine-HCI), a specific inhibitor of phospholipase C, on cyclic-GMP levels in human platelets was investigated. The concentrations of mepacrine producing 50% inhibition of human platelet aggregation induced by 5 microM ADP and 3 micrograms/ml of collagen were 50 +/- 8 and 70 +/- 15 microM, respectively. Addition of mepacrine to human platelet suspension resulted in increases in cyclic GMP. In contrast to cyclic-GMP levels, cyclic-AMP content was not affected by mepacrine. Mepacrine did not stimulate guanylate cyclase, but did specifically inhibit human platelet cyclic-GMP phosphodiesterase, separated from cyclic-AMP phosphodiesterase or other forms of phosphodiesterase on DEAE-cellulose columns. Stimulation by cyclic GMP of human platelet cyclic-GMP-stimulated cyclic-AMP phosphodiesterase activity was not inhibited by mepacrine. The IC50 value of the drug for cyclic-GMP phosphodiesterase was 40 microM, and IC50 for cyclic-AMP phosphodiesterase was 1.2 mM. Mepacrine was 30-times more potent as an inhibitor of human platelet cyclic GMP than of cyclic-AMP phosphodiesterase. Mepacrine blocks arachidonate release from human platelets by inhibiting phosphatidylinositol-specific phospholipase C. The increase in cyclic-GMP levels produced by addition of mepacrine will explain part of the pharmacological action of this drug.
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PMID:Mepacrine-induced inhibition of human platelet cyclic-GMP phosphodiesterase. 614 62

Amphibian oxyntic cells exposed by cryofracture were examined by field emission scanning electron microscopy. Comparisons were made between the structure thus revealed and those seen in thin-sectioned material from the same mucosas examined by transmission electron microscopy. Resting oxyntic cells had apical surfaces which were relatively smooth with some short microvilli. Apical cytoplasm was filled with smooth membrane tubules (so-called vesicotubules). Stimulation with a combination of histamine, dibutyryl cyclic AMP, and isobutylmethylxanthine (a phosphodiesterase inhibitor) led to a dramatic elaboration (i.e., increased membrane surface area) and a decrease in number of vesicotubules in the apical cytoplasm. The surface morphology of the stimulated oxyntic cell was much different from that reported for the mammalian parietal cell. Two types of surface elaboration were observed. Most commonly the surface was formed of flattened microplicae or lingulae. An irregular surface formed by the swelling of enlarged spaces near the apical surface was also observed. These new data have been used to evaluate the models which have been proposed to explain the nature of the transition from resting to stimulated morphology. A new model, which incorporates fusion of intracellular vesicotubules with each other and also with apical membrane, is proposed. The proposed fusion process may cause an increase in membrane area open to the extracellular (luminal)solution within the cell (rather than the eversion of membranes into the gastric lumen). Expansion of spaces between the microplicae may be caused by hydroosmotic pressures developed during active HCI secretion.
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PMID:Ultrastructural changes during stimulation of amphibian oxyntic cells viewed by scanning and transmission electron microscopy. 697 80

Inhibition of type IV phosphodiesterase (PDE IV) activity reduces the production of various proinflammatory cytokine and suppresses neutrophil activation. Nonsteroidal anti-inflammatory drugs such as aspirin induce gastric mucosal lesions. In the pathogenesis of aspirin-induced gastric mucosal lesion, the contributions, of activated inflammatory cells and proinflammatory cytokine production are critical. The specific PDE IV inhibitor rolipram is known to be a potent inhibitor of inflammation by increasing intracellular cyclic AMP in leukocytes. The aim of the present study was to determine whether rolipram can ameliorate aspirin-induced gastric mucosal lesions in rats and whether the agent can inhibit the inrease in neutrophil accumulation and the production of proinflammatory cytokines. Gastric lesions were produced by administration of aspirin (200 mg/kg) and HCI (0.15 N; 8.0 ml/kg). Rolipram was injected 30 min before aspirin administration. The tissue myeloperoxidase concentration in gastric mucosa was measured as an indicat or of neutrophil infiltration. The gastric mucosal concentrations of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) were determined by ELISA. The intragastric administration of aspirin induced multiple hemorrhagic erosions in rat gastric mucosa. Gastric mucosal lesions induced by aspirin were significantly inhibited by treatment with rolipram. The mucosal myeloperoxidase concentration was also suppressed by rolipram. Increases in the gastric content of TNF-alpha and IL-1beta after aspirin administration were inhibited by pretreatment with rolipram. We demonstrated that the specific type IV PDE inhibitor, rolipram, could have a potent antiulcer effect, presumably mediated by its anti-inflammatory properties.
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PMID:Rolipram, a specific type IV phosphodiesterase inhibitor, ameliorates aspirin-induced gastric mucosal injury in rats. 1598 61