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)

Ischaemia rapidly increases the concentration of cAMP in the brain by mechanism(s) which still remain undefined. In the present study significant enhancement of cAMP generation was found in vitro after brain ischaemia induced by decapitation or cardiac arrest. The particulate fraction from ischaemic brain accumulated considerably more cAMP and responded more effectively to stimulation by noradrenaline (NE), histamine (Hi) and adenosine than that prepared from normoxic controls. The most pronounced effect was observed immediately after ischaemic insult and proceeded to normalize during 24 hours of postischaemic recovery. The activation of cAMP production by NE and Hi, but not 2-chloradenosine (2-CA), was totally dependent on the presence of endogenous adenosine and calcium. The synergism of 2-CA with NE or Hi on cAMP accumulation was observed. Its disappearance after adenosine deaminase treatment indicates that the postischaemic activation of adenosine A2 receptors may be positively modulated by NE and Hi. These results strongly suggest that primary functional changes in the cell-membrane signalling system had been induced by the ischaemic insult.
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PMID:Rapid enhancement of cAMP accumulation in rat brain particulate fraction after ischaemia. 255 46

The sensitivity and responsiveness of adipocyte lipolysis to adenosine and pertussis toxin were studied in exercise-trained male rats. Exercise training (9 weeks of treadmill running) significantly increased lipolytic response of adipocytes to noradrenaline (NA). Addition of adenosine deaminase (ADA) to reaction mixture effectively enhanced NA-stimulated lipolysis in adipocytes from both conditioned rats. However, under these conditions, the difference due to exercise training was still evident, although the difference was less pronounced. The inhibition curves of the R-site adenosine analogue N6-phenylisopropyladenosine (PIA) against "basal" (lipolysis in the presence of ADA) and NA-stimulated lipolysis were almost comparable between two groups. Only a small (approx. 2-fold) increase in IC50 of adipocyte lipolysis was observed in each inhibition curve in exercise-trained rats. Within 120 min of addition of pertussis toxin to adipocytes from control rats, "basal" lipolysis was significantly increased as compared to "basal" lipolysis in the absence of toxin at the same point. Similarly, pertussis toxin significantly increased "basal" lipolysis in exercise-trained adipocytes. However these were relatively sensitive to pertussis toxin, since significant effect of toxin was seen within 60 min. An addition of NA (0.1 uM) to the medium in the presence of ADA and toxin significantly increased adipocyte lipolysis in both conditioned rats. Again, under these conditions, we observed that the maximal rate of lipolysis of adipocytes from exercise-trained rats was increased as compared to control rats. These results suggest that the decreased input through the inhibitory pathway in lipolytic cascade may be not rate limiting for the amplified lipolytic responsiveness of adipocytes to hormonal stimuli in exercise-trained rats.
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PMID:Effects of adenosine and pertussis toxin on lipolysis in adipocytes from exercise-trained male rats. 260 17

The effects of adrenaline, noradrenaline, and of the alpha 2- and beta-selective agonists clonidine and isoproterenol were studied in fifteen obese subjects before and after 4 weeks of caloric restriction (300 cal day-1). Basal glycerol release averaged 1.4 mumol (10(6) cells)-1 (180 min)-1 before starvation and 2.8 mumol (10(6) cells)-1 (180 min)-1 during starvation (P less than or equal to 0.1). Before starvation adrenaline and noradrenaline caused a 2-3-fold increase of glycerol release. This lipolytic effect disappeared during starvation. An inhibitory effect of adrenaline was observed instead which was maximal at an adrenaline concentration of 1 mumol 1(-1) (P less than or equal to 0.05). The dose-response relationships of the alpha 2- and beta-selective agents clonidine and isoproterenol were not appreciably changed by caloric restriction. The increase of basal lipolytic rate and the reversal of adrenaline action seen during caloric restriction could be mimicked by removal of endogenous adenosine using adenosine deaminase (1.6 microgram ml-1). In addition, inclusion of N6-phenylisopropyladenosine (1 mumol 1(-1)) into the medium reverted the adrenaline-induced inhibition seen during caloric restriction. The results suggest that local modulators such as adenosine are of primary importance for the apparent change of responsiveness to adrenaline and noradrenaline seen during starvation of human fat cells in vitro.
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PMID:Adrenergic regulation of lipolysis in abdominal adipocytes of obese subjects during caloric restriction: reversal of catecholamine action caused by relief of endogenous inhibition. 285 98

In slices of hippocampus from the rabbit, preincubated with [3H]noradrenaline and then continuously superfused, the modulation of the release of noradrenaline by adenosine receptors was studied. Electrical field stimulation of the slices elicited a release of [3H]noradrenaline which was inhibited in a concentration-dependent manner by various adenosine receptor agonists. From the order of potency: cyclohexyladenosine greater than (-)phenylisopropyladenosine [(-)PIA] greater than 5'-N-ethylcarboxamide-adenosine (NECA) greater than 2-chloro-adenosine greater than adenosine (+)phenylisopropyladenosine greater than ATP, the inhibitory adenosine receptor was classified as A1- (Ri-) receptor. The effect of the agonist was strongly reduced by adenosine receptor antagonists, the methylxanthines. A role for endogenous adenosine in the modulation of hippocampal noradrenaline release is supported by these findings: (1) that blockade of adenosine receptors by methylxanthines, especially by 8-phenyltheophylline, increased, whereas (2) inhibition of the uptake of adenosine decreased the evoked release of noradrenaline and (3) that deamination of endogenous extracellular adenosine by addition of adenosine deaminase to the medium enhanced the evoked transmitter release. Inhibitors of endogenous adenosine deaminase and 5'-nucleotidase were without effect. It is concluded that release of noradrenaline in the hippocampus is inhibited at the level of the noradrenergic nerve terminals by endogenous adenosine via A1 (or Ri) receptors.
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PMID:Adenosine: an endogenous modulator of hippocampal noradrenaline release. 299 2

Changes in adenosine 3',5'-cyclic monophosphate (cAMP) concentration were measured in cortical synaptosomes. Preincubation with adenosine deaminase reduced cAMP concentration by 45%. Oxotremorine, clonidine, gamma-aminobutyric acid (GABA) and baclofen produced no change in basal concentration. 2-Chloroadenosine and noradrenaline (NA), acting at beta-adrenoceptors, both caused a dose-dependent increase in cAMP; the NA-stimulated increase was depressed by GABA and by baclofen.
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PMID:The effect of presynaptic receptor stimulation on adenosine 3',5'-cyclic monophosphate concentrations in rat cortical synaptosomes. 300 40

The responsiveness of lipolysis to the stimulatory agonists noradrenaline, corticotropin and glucagon and to the inhibitory agonists N6-phenylisopropyladenosine, prostaglandin E1 and nicotinic acid was investigated with rat white adipocytes incubated with a high concentration of adenosine deaminase (1 unit/ml). The cells were obtained from fed or 48 h-starved euthyroid animals or from fed or starved animals rendered hypothyroid by 4 weeks of treatment with low-iodine diet and propylthiouracil. Hypothyroidism increased sensitivity to and efficacy of all three inhibitory agonists in their opposition of noradrenaline-stimulated lipolysis. Starvation decreased sensitivity to all three inhibitory agonists when opposing basal lipolysis. Hypothyroidism decreased sensitivity to noradrenaline, glucagon and corticotropin by 37-, 4- and 4-fold respectively and decreased the maximum response to these agonists by approx. 50%, 50% and 75% respectively. Starvation reversed decreases in maximum response to these agonists in hypothyroidism. Starvation in the euthyroid state increased sensitivity to glucagon and noradrenaline, but did not alter sensitivity to corticotropin. Cells from hypothyroid rats were relatively insensitive to Bordetella pertussis toxin, which substantially increased basal lipolysis in the euthyroid state.
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PMID:Sensitivity of adipocyte lipolysis to stimulatory and inhibitory agonists in hypothyroidism and starvation. 302 50

1. Adipocytes were isolated from the interscapular brown fat of male rats maintained at 21 degrees C. These animals were controls, streptozotocin-diabetics or 2-day insulin-treated diabetics. 2. With adipocytes from diabetic animals, maximum rates of noradrenaline-stimulated O2 uptake were decreased by 58%, and the Bmax. of [3H]GDP binding to mitochondria was decreased by 55%. Insulin administration reversed both of these changes. 3. Streptozotocin-diabetes increased basal lipolysis in adipocytes incubated with adenosine deaminase (1 unit/ml), decreased the EC50 (concn. giving 50% of maximum effect) for noradrenaline, but did not change the maximum rate of noradrenaline-stimulated lipolysis. Except for some small differences at very low concentrations (10-100 pM), diabetes or insulin treatment did not alter the sensitivity of noradrenaline-stimulated lipolysis or O2 uptake to the inhibitory effect of N6-phenylisopropyladenosine. It is therefore concluded that the lesion(s) in thermogenesis in diabetes are not attributable to any changes in lipolysis. 4. Blood flow through interscapular brown fat, measured by accumulation of [14C]DDT [14C-labelled 1,1,1-trichloro-2,2-bis-(p-chlorophenyl)ethane] was increased by 2.3-fold 70 min after a single administration of insulin to diabetic rats. This treatment decreased blood flow through epididymal white fat by 58%. 5. Propranolol treatment of diabetic rats muted the ability of insulin treatment to increase the maximum rate of noradrenaline-stimulated O2 uptake, suggesting that this action of insulin may be a secondary one rather than a direct effect of the hormone on the adipocytes.
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PMID:Factors influencing the altered thermogenic response of rat brown adipose tissue in streptozotocin-diabetes. 327 24

1. In helically cut strips of aorta from reserpine-treated guinea-pigs, cumulative concentrations (30 microM, 0.3 mM and 3 mM) of amrinone progressively reduced the basal tone of the preparations and relaxed the smooth muscle contracted by 1 microM noradrenaline or by 20 mM K+. 2. The relaxing effect was completely suppressed by tissue pretreatment with adenosine deaminase (1 U ml-1). 3. Relaxation induced by amrinone was not affected by 50 microM indomethacin or by 0.1 mM 8-phenyltheophylline and was potentiated by 5 microM quinidine. 4. Like amrinone, exogenous adenosine reduced the basal tone of the guinea-pig aorta strips and relaxed the preparations contracted by 1 microM noradrenaline or by 20 mM k+ in a concentration-dependent manner. 5. The relaxing activity of exogenous adenosine was not affected by 50 microM indomethacin, was potentiated by 5 microM quinidine and was partially antagonized by 0.1 mM 8-phenyltheophylline. 6. These results indicate the involvement of endogenous adenosine in the relaxing effect of amrinone on guinea-pig aorta strips, but the specific mechanism of amrinone-adenosine interaction remains to be elucidated.
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PMID:The response of isolated guinea-pig aorta to amrinone. 339 51

The effects of adenosine and of some products of its metabolic degradation on lipolysis were studied in rat fat cells isolated from epididymal adipose tissue. Basal glycerol release was not affected by adenosine and by uric acid, but it was significantly increased by inosine (1-100 microM) and by hypoxanthine (10-100 microM). Adenosine was more effective than inosine in antagonizing the lipolytic response of fat cells to theophylline. Also hypoxanthine and uric acid exerted a very potent, noncompetitive antagonism towards theophylline. Norepinephrine-induced lipolysis was inhibited by adenosine, hypoxanthine and uric acid approximately to the same extent, while inosine was ineffective at this level. Adenosine deaminase (0.5 U/ml) increased basal as well as theophylline- and norepinephrine-induced lipolysis. Moreover, adenosine deaminase enhanced the lipolytic rate in cells incubated with low (0.1, 1 microM) and, to a lesser extent, with high (10, 100 microM) inosine concentrations. These results suggest that inosine is the adenosine metabolite that may accumulate in the incubation medium following fat cell treatment with adenosine deaminase, thus contributing to the stimulatory effects of this enzyme on lipolysis.
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PMID:A reexamination of the effects induced by adenosine and its degradation products on rat fat cell lipolysis. 340 Dec 55

1. We have examined the effects of purinoceptor agonists and antagonists on the mechanical 'twitch' response, excitatory junction potential (e.j.p.) amplitude and [3H]-noradrenaline overflow in the mouse vas deferens. 2. The agonist profile for inhibition of the mechanical response was N6-([R]-2-phenylisopropyl)adenosine (L-PIA) congruent to N6-cyclohexyladenosine (CHA) greater than 5' N-ethylcarboxamido-adenosine (NECA) greater than 2-chloroadenosine (2ClA) congruent N6-([S]-2-phenylisopropyl)adenosine (D-PIA). 3. The P1-purinoceptor agonists inhibited the e.j.p. with an agonist profile of CHA greater than L-PIA congruent to NECA greater than 2ClA. 4. 2ClA inhibited [3H]-noradrenaline overflow with an EC50 of 1.2 microM which was not significantly different from the values for inhibition of the e.j.p. and the mechanical response. 5. The inhibitory action of 2ClA on the mechanical response was antagonized by 5 microM 8-phenyltheophylline (8-PT). However, neither blockade of P1-purinoceptors by 8-PT nor increasing the rate of degradation of endogenous adenosine by addition of adenosine deaminase had any effect on the mechanical response per se. 8-PT (5 microM) also failed to alter the e.j.p. amplitude or [3H]-noradrenaline overflow. 6. These results indicate that there are P1-purinoceptors present on sympathetic nerve terminals of the mouse vas deferens which are more like A1- than A2-receptors, but may be better classified as being of the A3-subtype (Ribeiro & Sebastiao, 1986). These receptors are not normally involved in the feedback regulation of transmitter release in this tissue.
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PMID:A study of the actions of P1-purinoceptor agonists and antagonists in the mouse vas deferens in vitro. 340 42


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