Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.5 (5'-nucleotidase)
 3,167 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the specific binding of 1,3,5(10)-estratrien-2,3,17 beta-triol (2-hydroxyestradiol) to an enriched membrane fraction isolated from the rat anterior pituitary gland. Specific [6,7-(3)H]2-hydroxyestradiol-17 beta ([3H]2-hydroxyestradiol) binding is saturable and displays a high and low affinity binding component. The apparent dissociation constants, KD, are 4 +/- 2 x 10(-10) and 2 x 10(-6) M with 13 fmol and 2.6 pmol bound/mg of protein, respectively. The specific high affinity binding increases linearly with increasing amounts of tissue protein. The binding is both temperature- and pH-dependent, with maximal binding at 37 degrees C and pH 7.4. The 2-hydroxyestradiol binding is shown to be stereospecific. Dopamine and spiroperidol (a dopamine antagonist) competitively inhibit the specific binding of [3H]2-hydroxyestradiol to the high affinity binding site with inhibition constants, KI, of 1 x 10(-6) M and 2 x 10(-5) M, respectively. Related catecholestrogens (2-hydroxyestrone and 2-hydroxyestriol) are also competitive inhibitors of [3H]2-hydroxyestradiol binding with KI values of 1.5 x 10(-5) M and 1.9 x 10(-5) M, respectively. None of the estrogens (estrone, estradiol, estriol) or 2-methoxyestrogen derivatives (2-methoxyestrone, 2-methoxyestradiol, 2-methoxyestriol) inhibits [3H]2-hydroxyestradiol binding at concentrations up to 10(-4) M. Norepinephrine, epinephrine, and serotonin are also ineffective as inhibitors at concentrations of 10(-5) M and inhibited less than 20% at 10(-4) M. Centrifugation through a stepwise discontinuous sucrose density gradient is used to separate subcellular components of the anterior pituitary cells. Approximately 90 per cent of the specific [3H]2-hydroxyestradiol binding is associated with the material at the 47.4 to 52.9% sucrose interface, the layer most highly enriched for 5'-nucleotidase (an enzyme marker for plasma membranes). Studies of tissue specificity indicate that specific 2-hydroxyestradiol binding sites are heterogeneously distributed in nervous tissue with the highest concentration of binding sites in the anterior pituitary, cerebral cortex, and hypothalamus and lower levels found in the thalamus and striatum. Low levels 2-hydroxyestradiol binding sites are also identified in liver and uterus. The present demonstration of specific 2-hydroxyestradiol binding to the anterior pituitary membrane provides information on the mechanism of catecholestrogen action.
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PMID:Binding of 2-hydroxyestradiol to rat anterior pituitary cell membranes. 743 Jan 5

Ecto-5'-nucleotidase (5'-ribonucleotide phosphohydrolase, EC 3.1.3.5) of mesangial cells may be the main source of adenosine within the glomerulus, and thus essential in the regulation of glomerular microcirculation. c-AMP and c-AMP-stimulating agents were found to induce ecto-5'-nucleotidase of mesangial cells. Dopamine is a catecholamine known to increase c-AMP levels in mesangial cells. We have studied the effect of dopamine on ecto-5'-nucleotidase expression and DNA synthesis of glomerular mesangial cells in culture. Human mesangial cells were exposed to dopamine in the concentration range from 0.1 microM- to 1 mM, for 6-72 h. Ecto-5'-nucleotidase activity of human mesangial cells increased from 118.6 +/- 7.7 to 171 +/- 12 nmol/min/mg in a 72 h culture. This effect was time- and dose-dependent. Cycloheximide, an inhibitor of protein synthesis did not modify basal 5'-nucleotidase activity but it suppressed the stimulatory effect of 10 microM dopamine. DNA synthesis of human mesangial cells, studied after exposure of these cells to the same concentrations of dopamine used in the 5'-nucleotidase stimulation, was inhibited, being also dose dependent. These results indicate that dopamine induces ecto-5'-nucleotidase and inhibits DNA synthesis of cultured human mesangial cells. This action of dopamine on glomerular mesangial cells may be important in the regulation of glomerular hemodynamics.
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PMID:Effect of dopamine on ecto-5'-nucleotidase expression in human glomerular mesangial cells. 800 38

Parkinson's disease (PD) is characterized by a progressive neurodegeneration in the substantia nigra and a striatal dopamine decrease. Striatal extracellular adenosine and ATP modulate the dopaminergic neurotransmission whereas guanosine has a protective role in the brain. Therefore, the regulation of their levels by enzymatic activity may be relevant to the clinical feature of PD. Here it was evaluated the extracellular nucleotide hydrolysis from striatal slices 4 weeks after a unilateral infusion with 6-OHDA into the medial forebrain bundle. This infusion increased ADP, AMP, and GTP hydrolysis by 15, 25, and 41%, respectively, and decreased GDP hydrolysis by 60%. There was no change in NTPDases1, 2, 3, 5, 6, and 5'-nucleotidase transcription. Dopamine depletion changes nucleotide hydrolysis and, therefore, alters the regulation of striatal nucleotide levels. These changes observed in 6-OHDA-lesioned animals may contribute to the symptoms observed in the model and provide evidence to indicate that extracellular purine hydrolysis is a key factor in understanding PD, giving hints for new therapies.
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PMID:The hydrolysis of striatal adenine- and guanine-based purines in a 6-hydroxydopamine rat model of Parkinson's disease. 2104 37