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)

Condensation products (CP) of the ethanol metabolite, acetaldehyde, and endogenous amines, such as dopamine and serotonin, have been proposed to be effectors of some symptoms of chronic ethanol use. Since hemostatic defects are known to occur in chronic ethanol use, the effects of CP on in vitro human platelet aggregation responses induced by several agents were determined. Both isoquinoline and beta carboline type CP significantly inhibited aggregation responses induced by epinephrine, with the concentrations to produce 50% inhibition ranging from 8-347 uM. The beta-carbolines significantly inhibited ADP-induced aggregation and also inhibited aggregation induced by collagen or arachidonic acid, but at high concentrations. Effects on epinephrine aggregation and ADP aggregation were reversible. Potential mechanisms of the inhibitory effects were briefly examined. Concomitant use of the phosphodiesterase inhibitor theophylline potentiated the effect of some but not other CP, possibly indicating an involvement of cyclic AMP. Concomitant use of the non-specific beta-adrenergic inhibitor propranolol had no effect on CP inhibition, indicating that CP probably do not stimulate platelet adenylyl cyclase-coupled beta 2-adrenoceptors. Thus, general inhibition by CP of platelet responses in the circulation is unlikely, except, possibly, for epinephrine-induced aggregation, because of the high concentrations of CP required. However, local regulation of platelet responses by release of stored CP during aggregation is possible since CP are stored in platelet dense granules.
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PMID:Effects of acetaldehyde condensation products on human platelet aggregation. 362 6

The chemical synthesis of the tital bridged trinucleoside diphosphates 3e and 3f along with the corresponding dinucleoside phosphates 3c and 3d is described. Bridged nucleosides 3a and 3b gave on treatment with triethyl orthoformate in the presence of p-toluenesulfonic acid in dimethylformamide the cyclic orthoesters 2a and 2b. Condensation of 2a and 2b with N,2',5'-O-triacetylcytidine 3'-phosphate (1) using dicyclohexylcarbodiimide in pyridine afforded after deblocking and chromatographic separation products 3c-f. The latter were readily degraded with pancreatic RNase, but 3c and 3e were completely resistant toward snake venom phosphodiesterase whereas 3d and 3f were digested to the extent of 65 and 43%, respectively. The major product of degradation of 3f with phosphodiesterase was compound 3d resulting from the combined action of phosphodiesterase and contaminating phosphomonoesterase. The results are explained in terms of stacking of terminal bridge nucleoside units in 3c-f. The implications of these findings for the function of snake venom phosphodiesterase are discussed.
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PMID:Synthesis of dicytidylyl-(3'-5')-1,2-di(adenosin-N6-yl)ethane and dicytidylyl-(3'-5')-1,4-di(adenosin-N6-yl)butane: covalently joined terminals of two transfer ribonucleic acids and their behavior toward snake venom phosphodiesterase. 624 71