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)

We measured urinary levels of total protein, N-acetyl-beta-D-glucosaminidase (NAG), alanine aminopeptidase, and adenosine deaminase-binding protein in ten children with osteogenic sarcoma who were receiving combination chemotherapy that included 12 doses of methotrexate (12 g/m2). Analysis of the changes in these sensitive markers of renal tubular damage permitted detection of subclinical methotrexate-induced nephrotoxicity. In the absence of cisplatin, methotrexate therapy was associated with significant but transient increases in each of the four markers. Irreversible nephrotoxicity, indicated by persistent rises in NAG and alanine aminopeptidase as well as increased serum creatinine levels, was associated with doses of methotrexate that followed the administration of cisplatin (400 mg/m2). The biphasic pattern of total protein and NAG excretion observed in all patients suggests more than one mechanism of methotrexate-induced nephrotoxicity. Monitoring renal tubular damage in patients who are receiving methotrexate in combined-drug regimens would provide useful information for scheduling nephrotoxic drugs in clinical trials.
Cancer 1986 Dec 15
PMID:Enhancement of methotrexate nephrotoxicity after cisplatin therapy. 287 29

The authors evaluated measurements of adenosine deaminase binding protein (ADB), a proximal renal tubular cell antigen, for detection of drug-induced tubular nephrotoxicity. Concentrations of ADB were determined immunochemically in serial urine specimens from 12 children who were receiving chemotherapy for malignant solid tumors. There was no indication of increased ADB excretion after administration of two nonnephrotoxic drugs, etoposide and doxorubicin, but in patients given the recognized nephrotoxins, cisplatin and methotrexate, or an investigational drug, ifosfamide, urinary concentrations of ADB increased greater than fivefold relative to baseline values. Increased ADB concentrations preceded cisplatin- or ifosfamide-induced elevations of serum creatinine. Results of the ADB assay correlated well with those obtained by enzymatic assays for N-acetyl-beta-D-glucosaminidase and alanine aminopeptidase (r = 0.76 and 0.53; n = 142, P less than 0.001) and marginally with total proteinuria (r = 0.21; P less than 0.02). Hence, serial ADB measurements may be useful in screening investigational drugs for acute subclinical nephrotoxicity.
Am J Clin Pathol 1986 Dec
PMID:Cancer chemotherapy-induced tubular nephrotoxicity evaluated by immunochemical determination of urinary adenosine deaminase binding protein. 287 4

Alkylxanthine drugs, such as theophylline, block adenosine receptors, inhibit phosphodiesterases and other enzymes, and cause the release of calcium from intracellular stores. Adenosine receptor blockade occurs at low micromolar concentrations of the drugs, while other effects occur in the millimolar concentration range. The effects of theophylline were tested on spontaneous transmitter release at the frog cutaneous-pectoris neuromuscular junction (NMJ). A change in the frequency, but not the amplitude, of miniature endplate potentials (mepps) was interpreted as a change in spontaneous transmitter release. In normal Ringer's, theophylline, at concentrations of 100 microM and 1 mM, theophylline had no consistent effect on spontaneous release. In contrast, theophylline produced dual effects on mepp frequency in hyperosmotic Ringer's. At 10 microM, theophylline depressed mepp frequency, while, at 100 microM and 1 mM, theophylline increased mepp rate. Since low micromolar concentrations of theophylline depressed spontaneous transmitter release, this action may result from adenosine receptor blockade and inhibition of a tonic, stimulatory effect of adenosine. This hypothesis was supported by the following experimental results: (1) Micromolar concentrations of theophylline reversed the effects of applied adenosine on neuromuscular transmission. (2) The inhibitory effect of theophylline was mimicked by 2 other alkylxanthines, 8-phenyltheophylline and 8-p-sulfophenyltheophylline. These drugs may be more specific adenosine receptor antagonists than theophylline. (3) The inhibitory effect of theophylline was mimicked by adenosine deaminase, an enzyme that breaks down and inactivates adenosine. (4) The depressant action of theophylline was masked by the addition of adenosine deaminase to the hyperosmotic Ringer's. Application of adenosine to the frog NMJ reduces spontaneous transmitter output.(ABSTRACT TRUNCATED AT 250 WORDS)
J Neurosci 1988 Dec
PMID:Dual effects of theophylline on spontaneous transmitter release from frog motor nerve terminals. 290 89

The adenosine hypothesis of local metabolic control of coronary blood flow was tested in the unstressed heart with adenosine deaminase, which converts adenosine to nonvasoactive inosine. If adenosine is normally an important physiological regulator, then adenosine deaminase should lower coronary blood flow. The left main coronary artery was perfused at constant pressure in anesthetized, closed-chest dogs. Adenosine deaminase was deposited in one region of the left ventricle by selective infusion into a branch of the left coronary artery. Coronary blood flow measured with radioactive microspheres was not lower in the region treated with adenosine deaminase than flow measured simultaneously in an untreated control region of the same heart. This finding is contrary to the prediction of the adenosine hypothesis. Coronary vasodilation elicited by intracoronary adenosine infusion was inhibited in the adenosine deaminase-treated region compared with the control region, indicating that adenosine deaminase lowered adenosine concentration at the vascular adenosine receptor. Inhibition of exogenous adenosine vasodilation was fully reversed by intracoronary infusion of a specific inhibitor of adenosine deaminase. Measurement of adenosine deaminase activity in cardiac lymph provided evidence that adenosine deaminase reached the myocardial interstitial space. These results demonstrate that introducing adenosine deaminase into the interstitial space of the unstressed heart did not lower coronary blood flow. This finding indicates that adenosine is normally below the vasoactive threshold and therefore is not important in mediating local metabolic control of blood flow in the unstressed heart.
Am J Physiol 1985 Dec
PMID:Adenosine is unimportant in controlling coronary blood flow in unstressed dog hearts. 300 Jan 96

Patients with tumors secreting vasoactive intestinal peptide (VIP) often develop hyperglycemia and glucose intolerance. Although VIP has been reported to increase glucose output by the liver, the concentration required for this effect greatly exceeds that observed clinically. We therefore investigated the effects of VIP on insulin-stimulated glucose transport in isolated adipocytes. Inhibition of insulin action was observed at a concentration of 1 ng/ml VIP with half-maximal inhibition at approximately 20 ng/ml. 125I-VIP bound to specific high-affinity sites on the adipocytes. Fifty percent inhibition of binding occurred at a concentration of unlabeled VIP of approximately 10 ng/ml and was not affected by insulin, glucagon, or growth hormone. As we have observed previously with glucagon and catecholamines, inhibition of insulin action by VIP was observed only when accumulation of adenosine in the incubation medium was prevented by addition of adenosine deaminase. Under these conditions VIP markedly increased cellular cAMP levels. A good correlation was observed among VIP binding, inhibition of insulin-stimulated glucose transport, and cellular concentrations of cAMP. The results suggest that inhibition of insulin action in adipose tissue contributes to the hyperglycemic effect of VIP. Together, with our published findings on glucagon and catecholamines, these results support the hypothesis that counterregulatory hormones inhibit insulin action by increasing cellular concentrations of cAMP.
Am J Physiol 1985 Dec
PMID:Vasoactive intestinal peptide inhibits insulin-stimulated glucose transport in rat adipocytes. 300 79

The activity of 5'-nucleotidase, AMP deaminase, adenosine deaminase, acid phosphatase, alkaline phosphatase and nucleotide pyrophosphatase was assayed in human thyroid glands. The 5'-nucleotidase activity was higher than that of AMP deaminase which suggested that AMP undergoes degradation primarily as a result of dephosphorylation in thyroid tissue. A high acid phosphatase activity was noted as compared to that of alkaline phosphatase activity. In toxic goitre the increase in adenosine deaminase and acid phosphatase was observed together with the decrease in pyrophosphatase activity.
Endocrinol Exp 1985 Dec
PMID:Activity of 5'-nucleotidase, AMP deaminase, adenosine deaminase, acid and alkaline phosphatase and nucleotide pyrophosphatase in human thyroid. 300 51

Adenosine deaminase reversibly increased the amplitude and the quantum content of the end-plate potentials (EPPs) recorded from superficial muscle fibers of frog sartorius preparations in which twitches have been prevented with high-magnesium solutions. Adenosine deaminase prevented the inhibitory effect of exogenously applied adenosine but not that of 2-chloroadenosine on the amplitude of EPPs. The effect of adenosine deaminase was abolished by erythro-9(2-hydroxy-3-nonyl)adenine (EHNA). The results suggest that endogenous adenosine exerts an inhibitory 'tone' over neuromuscular transmission.
Neurosci Lett 1985 Dec 04
PMID:Enhancement of transmission at the frog neuromuscular junction by adenosine deaminase: evidence for an inhibitory role of endogenous adenosine on neuromuscular transmission. 300 27

Activation of rat adipocyte R1 adenosine receptors by phenylisopropyladenosine (PIA) decreased cyclic AMP and lipolysis; this effect was blocked in cells from pertussis-toxin-treated rats. In contrast, the ability of 2',5'-dideoxyadenosine to decrease cyclic AMP was not affected by pertussis-toxin treatment. Addition of adenosine deaminase to the medium in which adipocytes from control animals were incubated resulted in activation of lipolysis. Interestingly, adipocytes from toxin-treated rats (which had an already increased basal lipolysis) responded in an opposite fashion to the addition of adenosine deaminase, i.e. the enzyme decreased lipolysis, which suggested that adenosine might be increasing lipolysis in these cells. Studies with the selective agonists N-ethylcarboxamidoadenosine (NECA) and PIA indicated that adenosine increases lipolysis and cyclic AMP accumulation in these cells and that these actions are mediated through Ra adenosine receptors. Adenosine-mediated accumulation of cyclic AMP was also observed in cells preincubated with pertussis toxin (2 micrograms/ml) for 3 h. In these studies NECA was also more effective than PIA. Our results indicate that there are three types of adenosine receptors in fat-cells, whose actions are affected differently by pertussis toxin, i.e. Ri-mediated actions are abolished, Ra-mediated actions are revealed and P-mediated actions are not affected.
Biochem J 1985 Dec 01
PMID:Rat fat-cells have three types of adenosine receptors (Ra, Ri and P). Differential effects of pertussis toxin. 300 5

We studied purine metabolism in rheumatoid arthritis (RA), adenosine deaminase (ADA), 5'-nucleotidase (5'NU) and purine nucleoside phosphorylase (PNP) activities by measuring the circulating mononuclear cells of patients with RA and healthy controls. Patients had significantly lower levels of ADA and 5'NU but not of PNP than controls. The decreases could not be related to age, antiinflammatory therapy, decreased percentages of T cells or imbalance between major T cells subsets. Differences in cell maturation or traffic could account for our observation. Alternatively, abnormalities of purine metabolism are not definitely excluded in RA if the lower enzyme activity is not sufficient to perform the metabolic steps.
J Rheumatol 1985 Dec
PMID:Purine enzyme levels in rheumatoid arthritis. 300 61

Investigations were carried out to demonstrate the function and the possible advantage of the interplay between beta 1 and alpha 2 adrenoceptor sites in the regulation of human subcutaneous fat-cell lipolysis. alpha 2 and beta adrenoceptor binding studies were conducted with antagonist radioligands and revealed that alpha 2-adrenoceptors ([3H]yohimbine and [3H]rauwolscine binding sites) are more numerous than beta 1-adrenoceptors ([3H]dihydroalprenolol and [3H]CGP-12177 binding sites) in human fat-cell membranes. Physiological agonists epinephrine and norepinephrine competed with [3H]-ligand sites with a higher affinity for alpha 2 sites than for beta 1 sites. Epinephrine exhibited a higher affinity than norepinephrine for the alpha 2 sites; the two amines had the same affinity for beta 1 sites. In lipolysis studies conducted in the absence of adenosine deaminase the beta lipolytic action of the biological amines predominated; after alpha 2-adrenoceptor blockade by yohimbine or idazoxan, the amines exhibited an intrinsic activity similar to that of isoproterenol. When adenosine was prevented from accumulating in the incubation medium by inclusion of adenosine deaminase, low concentrations of epinephrine and norepinephrine preferentially exerted an antilipolytic action. We conclude that: he lipolytic response in abdominal human subcutaneous fat cells to physiological amines results from the interplay between beta 1-and alpha 2-adrenoceptor stimulation; alpha 2 adrenoceptors, with their higher number and higher affinity for the physiological amines, and the adrenoceptor population involved at the lowest (i.e. physiological) concentrations of the amines.(ABSTRACT TRUNCATED AT 250 WORDS)
Eur J Clin Invest 1985 Dec
PMID:Evidence that epinephrine acts preferentially as an antilipolytic agent in abdominal human subcutaneous fat cells: assessment by analysis of beta and alpha 2 adrenoceptor properties. 300 59


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