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

Isolated rat fat cells were incubated at pH 8.5 in order to delay PGI2 inactivation. Nicotinic acid, at concentrations lower than 2 mM was ineffective in antagonizing the stimulation of lipolysis induced by norepinephrine (2 microM). The potentiation of norepinephrine effect due to PGI2 (0.1 microM) was abolished by 0.1 mM nicotinic acid and, at higher concentrations of the drug, the rate of the process fell below the one measured in the absence of PGI2, with a resulting decrease of the response to norepinephrine. Nicotinic acid (0.04-0.4 mM) antagonized the stimulation of lipolysis caused by adenosine deaminase (0.5 U/ml) or by theophylline (0.5 mM) and the potentiation of norepinephrine effect due to adenosine deaminase. In cells treated with adenosine deaminase (0.5 U/ml) or with theophylline (0.5 mM), PGI2 (40 nM) inhibited the lipolytic effect of norepinephrine (5 microM) and nicotinic acid acted synergistically with PGI2 at this level. These results indicate that the antilipolytic action of nicotinic acid is influenced by endogenous adenosine and is increased by PGI2.
 ...
PMID:Influence of prostacyclin on the antilipolytic effect of nicotinic acid in rat fat cells: a comparison with adenosine deaminase and theophylline. 331 35

Dipyridamole was initially introduced as a coronary vasodilator. The exact mechanism of action of dipyridamole on the coronary vasculature is unknown, but proposed mechanisms of action include inhibition of adenosine uptake, increased myocardial prostacyclin production and inhibition of phosphodiesterase activity. The purpose of our study was to examine the electrophysiological effects of dipyridamole on guinea-pig papillary muscles and canine cardiac Purkinje fibers to determine whether similar mechanisms might account for the electrophysiological effects of this compound. Conventional microelectrode techniques were used to record transmembrane action potentials from either guinea-pig papillary muscles or canine cardiac Purkinje fibers. Dipyridamole produces a dose-dependent prolongation of action potential duration with a threshold concentration of approximately 5 X 10(-7) M in tissues from either species. Dipyridamole (10(-5) M) increases action potential amplitude (124 +/- 1 to 127 +/- 1 mV), increases action potential duration (119 +/- 6 to 146 +/- 5 msec) and produces hyperpolarization of the resting potential (-85 +/- 1 to -87 +/- 1 mV) in guinea-pig papillary muscles (n = 27, P less than .05). Dipyridamole (10(-5) M) increases action potential duration (276 +/- 5 to 293 +/- 5 msec) in canine cardiac Purkinje fibers (n = 21, P less than .05). The effects of dipyridamole (5 X 10(-7) M) are neither accentuated by adenosine (10(-4) M) nor attenuated by adenosine deaminase (1 U/ml) Pretreatment with indomethacin (10(-5) M) does not block these effects. Dipyridamole (10(-5) M) produces a negative chronotropic response in canine Purkinje fibers, increases mean escape intervals from 4.9 +/- 0.9 to 7.8 +/- 1.4 sec (n = 8, P less than .05) and fails to suppress slow response action potentials in 22 mM K+ depolarized tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Adenosine and prostacyclin independent electrophysiological effects of dipyridamole in guinea-pig papillary muscles and canine cardiac Purkinje fibers. 609 2

The hypothesis was investigated that myocardial hypoxia stimulates the production of platelet anti-aggregatory substances in the heart. Rabbit hearts were perfused under normoxic or hypoxic conditions and the coronary and interstitial effluents from the hearts were separated. The occurrence of anti-aggregatory activity (AAA) in the interstitial effluent was detected in vitro from its capacity to inhibit ADP-induced platelet aggregation. The AAA in the effluent was deemed to be prostacyclin (PGI2) if its release was abolished by administration of indomethacin (5 X 10(-5) M) to the heart, and to be adenosine if it was abolished by incubation of the effluent with adenosine deaminase. During normoxic perfusion, only a minor efflux of AAA appeared from the heart; neither was the efflux appreciable during mild hypoxia (30 or 60% O2). Severe hypoxia (venous pO2 below 5 kPa), on the other hand, was associated with a marked release of AAA. Incubation of hypoxic effluent with adenosine deaminase resulted in a small loss of activity, indicating that the major part of the AAA was not ascribable to adenosine. After indomethacin treatment, significant amounts of AAA still appeared in the effluent during hypoxia. However, unlike the case before indomethacin, this AAA was completely destroyed by adenosine deaminase. From these data, we conclude that myocardial hypoxia can mobilize either of two independent mechanisms for protection against platelet aggregation: an activation of the synthesis and release of prostacyclin, and a more complete breakdown of ATP, leading to an increased formation and efflux of adenosine.
 ...
PMID:Hypoxia elicits liberation of anti-aggregatory substances from isolated rabbit hearts. 635 93

In rat fat cells incubated for 15 min at 37 degrees and pH 8.5, glycerol release was highly stimulated both by norepinephrine and by theophylline. Prostacyclin (PGI2) (10(-8)-10(-7)M) did not alter the basal rate of glycerol release but potentiated the lipolytic effect of 2 X 10(-6)M norepinephrine. The rate of norepinephrine-induced glycerol release was increased by PGI2 during 10 min of incubation and then maintained for the next 5 min. Lipolysis induced by concentrations of norepinephrine which produced maximal effects was not altered by PGI2. PGI2 (10(-7)-10(-6)M) also potentiated the effect of 5 X 10(-4)M theophylline on glycerol release, but antagonized the stimulation induced by a maximally effective concentration of the methylxanthine (2 X 10(-3)M). Incubation of the cells with norepinephrine in the presence of 2 X 10(-4) or 5 X 10(-4)M theophylline caused a loss of the potentiating effect of PGI2 on norepinephrine-induced lipolysis. In the presence of 10(-3)M theophylline, the lipolytic action of norepinephrine was inhibited by PGI2. In fat cells incubated with adenosine deaminase (0.5 U/ml), 2.5 X 10(-7)M PGI2 did not alter the response to 5 X 10(-4)M theophylline and inhibited the effect of norepinephrine both in the absence and in the presence of theophylline. The present results show that, under appropriate experimental conditions, PGI2 may act as a lipolytic agent in isolated fat cells and that some kind of interaction exists between stimulation of methylxanthine-sensitive adenosine receptors and stimulation of PGI2 receptors.
 ...
PMID:Prostacyclin and lipolysis in rat fat cells. 639 92

The present study was designed to clarify the reason why rat platelets obtained from arterial blood show a less marked aggregation than those obtained from venous blood, and to investigate the contribution of the vessel wall to this phenomenon. Incubation of arterial or venous platelet-rich plasma (PRP) with papaverine, a phosphodiesterase blocker, resulted in a more marked inhibition of the aggregation parameters for arterial than for venous PRP, indicating that a cAMP-dependent mechanism is involved. Incubation of PRP in vitro with adenosine deaminase did not significantly modify aggregation. Rats treated in vivo with different doses of acetylsalicylic acid or of tranylcypromine, two cyclo-oxygenase inhibitors, abolished the aggregation differences between arterial and venous PRP. It is suggested that this difference in platelet behavior may be due to a mechanism dependent on a PGI2-like, probably cAMP-related activity in which the heart and/or the lungs may play an important role.
 ...
PMID:What's provoking different aggregation between arterial and venous platelets in the rat? 644 10

ATP is a well-known inducer of prostacyclin and nitric oxide release from vascular endothelial cells. These responses are mediated by P2 receptors coupled to a phospholipase C. We have investigated the influence of ATP on the control of adenosine 3',5'-cyclic monophosphate (cAMP) in bovine aortic endothelial cells. ATP produced a slight increase in the cAMP content of unstimulated endothelial cells. A more impressive response to ATP (5-fold) was observed in forskolin-stimulated cells. The rank orders of potency of various ATP analogues were strikingly different for the increase in cAMP and the accumulation of inositol phosphates. The action of ATP was unaffected by indomethacin. Protein kinase C downregulation produced only a partial inhibition of the ATP response. The effect of phorbol 12-myristate 13-acetate and bradykinin on the forskolin-induced accumulation of cAMP was much smaller than that of ATP. Neither adenosine deaminase nor AMP deaminase decreased the response to ATP, which thus cannot result from the ATP degradation into adenosine. However, 8-(p-sulfophenyl)theophylline inhibited the responses to both ATP and adenosine. In conclusion, ATP enhances the accumulation of cAMP in endothelial cells. This action appears to be the sum of two components: a minor one resulting from kinase C activation and a major one mediated either by a direct interaction of ATP with A2 receptors, or by putative methylxanthine-sensitive P2 receptors.
 ...
PMID:Enhancement of endothelial cAMP accumulation by adenine nucleotides: role of methylxanthine-sensitive sites. 838 57

In the perfused guinea-pig heart reactive hyperaemia (RH) after occlusion of coronary flow (1-60 s) was inhibited by 100-60% with NG-nitro-L-arginine (100 microM) and to a lesser extent (by 35%) after 8-phenyltheophylline (10 microM), but not by indomethacin (5 microM). Inhibition of adenosine deaminase by erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) (5 microM) not only increased the concentration of adenosine in the coronary perfusate, but also prolonged the duration of RH. RH induced cardiac generation of prostacyclin, nitric oxide and adenosine as indicated by the appearance of 6-keto-PGF1 alpha, cyclic GMP, adenosine, inosine, hypoxanthine, xanthine and urate in the perfusate. Only NO and adenosine, but not prostacyclin, were responsible for RH. RH after short-term (1-10 s) coronary occlusion was mediated by NO, whereas adenosine and NO maintained RH that followed after longer (20 s-10 min) periods of cardiac ischaemia. Prostacyclin never participated in the mediation of RH.
 ...
PMID:Ischaemic cardiac hyperaemia: role of nitric oxide and other mediators. 908 46

The metabolites that mediate coronary reactive hyperemia have not been definitely identified. Although adenosine and endothelium derived substances seem to be involved, their relative contributions have not been defined yet. In the canine coronary circulation, we studied the relative participation of adenosine, nitric oxide and prostacyclin in reactive hyperemia, by measuring the changes produced by interfering with the synthesis or action of these metabolites. The dose-response curve for flow changes vs intracoronary administration of adenosine was displaced to the right after the inhibition of nitric oxide synthesis with N-omega-nitro-L-arginine, revealing that nitric oxide release partly mediates the vasodilator action of adenosine. The inhibition of PGI-2 synthesis with indomethacin did not modify reactive hyperemia. Interference with adenosine action, by administration of adenosine deaminase plus theophylline, decreased reactive hyperemia by 31.0 +/- 4.0% (p < 0.001). Inhibition of nitric oxide synthesis decreased reactive hyperemia by a larger (p < 0.005) magnitude, 41.0 +/- 3.9% (p < 0.001), revealing the existence of other stimuli for nitric oxide release in reactive hyperemia besides adenosine. Simultaneous inhibition of nitric oxide and PGI-2 syntheses and of adenosine action reduced reactive hyperemia, but the effect was not additive, reaching 49.5 +/- 4.5% of control. Since nitric oxide and adenosine are the most important mediators in reactive hyperemia so far described, our results suggest that other metabolites, acting directly or through mediators other than adenosine or nitric oxide, are responsible for about 50% of coronary reactive hyperemia.
 ...
PMID:Relative participation of adenosine and endothelium derived mediators in coronary reactive hyperemia in the dog. 925 46

The aim of this study was to investigate and clarify the role of prostaglandins (PG) on fat cell lipolysis in female rats. Incubations with adenosine deaminase (ADA) were used for the deamination of endogenous adenosine and increased basal (155%) and isoproterenol (10(-9) M) (348%) stimulation of glycerol release from adipocytes. Indomethacin and aspirin increased the effects of ADA while indomethacin further increased isoproterenol (with ADA) stimulation of lipolysis (p < or = 0.05). Exogenous PGE2 and PGI2 inhibited the isoproterenol and ADA stimulation of fat cell lipolysis (p < or = 0.05). The expected stimulatory effect of high concentrations of PGE2 and of low concentrations of PGI2 was not observed in the presence of ADA. Dose-response curves revealed that the inhibitory effects of PGs were reached at lower concentrations for PGE2 than for PGI2 (p < or = 0.05). In conclusion, this study showed that endogenous and exogenous PGs of adipose tissue only express an antilipolytic action on fat cell lipolysis. This effect appears to be highly significant when the beta-adrenergic pathway is stimulated. Our results also stress the need to control the antilipolytic effects of adenosine to study the regulation of fat cell lipolysis by PGs.
 ...
PMID:The lack of bimodality in the effects of endogenous and exogenous prostaglandins on fat cell lipolysis in rats. 967 20