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)

A reserpine-like agent, 2-hydroxy-2-ethyl-3-isobutyl-9,10-dimethoxy-1,2,3,4,6,7,-hexa-hydro-11b-H-benzo[a]quinolizine (BQZ), at concentrations that do not inhibit phosphodiesterase activity, produces a marked increase in the outflow of 3-H-dihydroxyphenyl-ethyleneglycol from the isolated, perfused cat slpeen prelabeled with 3-H-norepinephrine (3-H-NE). The increased intraneuronal levels of catechols probably account for the inhibition of the conversion of 1-minus14C-L-tyrosine to 1-minus14C-L-dopa which is observed in the presence of the drug. In addition, in the presence of 0.9 muM BQZ, there is a 2.5- to 3-fold increase in the nerve stimulation-mediated overflow of NE, 3-H-NE, total 3-H and dopamine-beta-hydroxylase activity. A highly significant positive correlation was observed between the increase in the spontaneous release of 3-H and the enhanced exocytotic release of transmitter by nerve stimulation. These results suggest that either a primary alteration of the storage granule membrane or the subsequent enhanced intraneuronal levels of NE or NE metabolites may be responsible for the enhanced exocytotic release by nerve stimulation. In the presence of 0.9 muM BQZ, addition of 3 muM cocaine produces an increase in the nerve stimulation-mediated overflow of NE and an inhibition of the formation of 3-H-dihydroxyphenylethyleneglycol. In addition, there is a 20 to 30% decrease in the overflow of 3-H and dopamine-beta-hydroxylase activity and a marked delay in the outflow of the enzyme elicited by nerve stimulation. These results suggested that, in the presence of BQZ, a large fraction of the NE released during nerve stimulation is recaptured into the nerve terminals where it is subsequently metabolized to 3-H-dihydroxyphenylethyleneglycol. The enhanced exocytotic release of NE, the extensive presynaptic metabolism of the recaptured transmitter subsequent to release by nerve stimulation, and inhibition of norepinephrine synthesis all appear to contribute to the accelerated depletion of tissue NE which is observed when the splenic nerves are stimulated in the presence of 0.9 muM BQZ. These results provide an explanation for the accelerated depletion of tissue NE in animals treated with reserpine-like compounds when the sympathetic innervation is intact.
 ...
PMID:Release of norepinephrine and dopamine-beta-hydroxylase by nerve stimulation. V. Enhanced release associated with a granular effect of a benzoquinolizine derivative with reserpine-like properties. 23 14

The stability of phosphotriester derivatives of 3'-azido-2',3'-dideoxythymidine (AZT) bearing a S-pivaloyl-2-thioethyl (tBuSATE) group and various aryl residues derived from L-tyrosine was evaluated in biological media. The results demonstrate that such compounds give rise to intracellular delivery of the parent mononucleotide through esterase and phosphodiesterase hydrolytic steps, successively.
 ...
PMID:SATE (aryl) phosphotriester series. II. Stability studies and physicochemical parameters. 1456 8

Three different phosphatases ("slow", "middle" and "fast") were found in Amoeba proteus (strain B) after PAGE and a subsequent gel staining in 1-naphthyl phosphate containing incubation mixture (pH 9.0). Substrate specificity of these phosphatases was determined in supernatants of homogenates using inhibitors of phosphatase activity. All phosphatases showed a broad substrate specificity. Of 10 tested compounds, p-nitrophenyl phosphate was a preferable substrate for all 3 phosphatases. All phosphatases were able to hydrolyse bis-p-nitrophenyl phosphate and, hence, displayed phosphodiesterase activity. All phosphatases hydrolysed O-phospho-L-tyrosine to a greater or lesser degree. Only little differences in substrate specificity of phosphatases were noticed: 1) "fast" and "middle" phosphatases hydrolysed naphthyl phosphates and O-phospho-L-tyrosine less efficiently than did "slow" phosphatase; 2) "fast" and "middle" phosphatases hydrolysed 2- naphthyl phosphate to a lesser degree than 1-naphthyl phosphate 3) "fast" and "middle" phosphatases hydrolysed O-phospho-L-serine and O-phospho-L-threonine with lower intensity as compared with "slow" phosphatase; 4) as distinct from "middle" and "slow" phosphatases, the "fast" phosphatase hydrolysed glucose-6-phosphate very poorly. The revealed broad substrate specificity of "slow" phosphatase together with data of inhibitory analysis and results of experiments with reactivation of this phosphatase by Zn2+-ions after its inactivation by EDTA strongly suggest that only the "slow" phosphatase is a true alkaline phosphatase (EC 3.1.3.1). The alkaline phosphatase of A. proteus is secreted into culture medium where its activity is low. The enzyme displays both phosphomono- and phosphodiesterase activities, in addition to supposed protein phosphatase activity. It still remains unknown, to which particular phosphatase class the amoeban "middle" and "fast" phosphatases (pH 9.0) may be assigned.
 ...
PMID:[Substrate specifity in Amoeba proteus]. 1708 51