Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Analysis of cyclic nucleotide phosphodiesterase (PDE) activity in cellular fractions from cultured rat pheochromocytoma (PC12) cells has shown that the predominant hydrolytic activity in both cytosolic and particulate compartments is characteristic of a PDE II, the cGMP-activatable family of PDE isozymes. Cytosolic PDE activity was purified to a high degree utilizing DE-52 anion exchange and cGMP-Sepharose affinity chromatographies. The physicochemical properties of PC12 PDE II were similar to those of PDE II isolated from particulate or soluble fractions of other tissues, including subunit molecular weight of approximately 102,000, activation of cAMP hydrolysis by cGMP, and positive cooperative kinetic behavior for cAMP and cGMP hydrolysis. The potential role of PDE II in regulating cAMP metabolism in intact PC12 cells was studied using an [3H]adenine prelabeling technique. Stimulation of PC12 cell adenosine receptors resulted in a 5-8-fold increase in cAMP accumulation. Removal of the adenosine stimulus by the addition of exogenous adenosine deaminase resulted in a rapid decay of cAMP to prestimulated basal levels within 2 min. Treatment of PC12 cells with atrial natriuretic factor or sodium nitroprusside caused 1) increased intracellular cGMP levels, 2) attenuation of adenosine-stimulated cAMP accumulation, and 3) increased rates of cAMP decay after removal of the adenosine stimulus. Treatment of PC12 cells with HL-725 (a potent inhibitor of isolated PDE II activity in vitro) caused 1) increased basal cAMP accumulation, 2) potentiation of adenosine-stimulated cAMP accumulation, and 3) retardation of the rate of cAMP decay after removal of the adenosine stimulus. HL-725 blocked both the attenuation of cAMP accumulation and the accelerated rate of cAMP decay observed with the cGMP-elevating agents. These results suggest that, in PC12 cells, drugs or hormones that inhibit PDE II or increase intracellular cGMP levels to activate PDE II can modulate cAMP metabolism by altering the catalytic status of the enzyme.
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PMID:Phosphodiesterase II, the cGMP-activatable cyclic nucleotide phosphodiesterase, regulates cyclic AMP metabolism in PC12 cells. 164 46

The hyperfiltration action of atrial natriuretic factor (ANF) and glucagon is accompanied by an elevation of adenosine in urine. We employed adenosine deaminase to evaluate the role of intrarenal adenosine in glomerular hyperfiltration induced by those hormones. Administration of ANF (2 micrograms/kg/min) resulted in an increase in the glomerular filtration rate (GFR): 1.99 vs. 3.01 ml/min (p less than 0.02) which was associated with a rise of adenosine excretion 87 vs. 151 pmol/min. Similarly, infusion of glucagon (2 micrograms/kg/min) raised the GFR from 1.86 to 2.67 ml/min (p less than 0.02) and adenosine excretion from 105 to 178 pmol/min (p less than 0.02). Adenosine deaminase treatment (2 U x kg/min) did not change the basal GFR and renal plasma flow but decreased plasma adenosine level 0.64 vs. 0.18 microM (p less than 0.001) and its excretion: 93 vs. 13 pmol/min (p less than 0.01). In adenosine deaminase treated rats ANF dramatically increased the GFR from 2.09 to 4.18 ml/min (p less than 0.001) and fractional filtration from 0.29 to 0.57, and the increase persisted throughout infusion of ANF. Similarly, adenosine deaminase treatment potentiated and prolonged the effect of glucagon on the GFR. These data indicate that depletion in renal adenosine does not decrease the GFR and that adenosine is present at inhibitory concentrations only during hormonal stimulation of glomerular filtration. It is concluded that renal endogenous adenosine functions do restrain hyperfiltration induced by ANF or glucagon.
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PMID:Intrarenal adenosine prevents hyperfiltration induced by atrial natriuretic factor. 213 65