Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.5.4.4 (adenosine deaminase)
5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent evidence suggests that ethanol initially causes an increase in receptor-dependent cAMP levels, followed by heterologous desensitization of receptors coupled to GS after chronic exposure. Here we investigated the role of adenosine in mediating these responses. We found that ethanol caused accumulation of extracellular adenosine in NG108-15 and S49 lymphoma cells. This adenosine activated adenosine receptors to increase intracellular cAMP levels. The addition of adenosine deaminase, to degrade accumulated extracellular adenosine, or isobutyl-methylxanthine, an adenosine receptor antagonist, completely blocked ethanol-induced increases in cAMP levels in NG108-15 cells. Chronic exposure of NG108-15 and S49 wild type cells to ethanol resulted in heterologous desensitization of adenosine receptor- and prostaglandin E1 receptor-dependent cAMP signal transduction. Coincubation of NG108-15 and S49 wild type cells with adenosine deaminase and ethanol for 48 hr prevented heterologous desensitization. Moreover, mutant S49 cells, which are unable to transport adenosine, did not accumulate extracellular adenosine after incubation with ethanol and did not develop ethanol-induced heterologous desensitization. Our results suggest that adenosine is an important mediator of both the acute and chronic effects of ethanol on cAMP signal transduction.
...
PMID:Adenosine is required for ethanol-induced heterologous desensitization. 255 72

Hormone-stimulated lipolysis is reduced in genetically obese rodents and may contribute to the increased adiposity characteristic of the obese state. Endogenously released adenosine, acting via the A1 receptor coupled to the inhibitory guanosine 5'-triphosphate binding protein, Gi, provides a tonic inhibition of lipolysis in rat adipocytes. Removal of this inhibition by the addition of adenosine deaminase frequently results in maximal lipolytic activity. Adipocytes isolated from lean Zucker (Fa/?) rats responded normally to adenosine deaminase, where lipolysis in adipocytes from obese Zucker (fa/fa) rats remained approximately 50% inhibited. Adipocyte adenylate cyclase was equally responsive to activation by forskolin, but lipolytic hormones were significantly less effective in stimulating adenosine 3',5'-cyclic monophosphate (cAMP) production in the obese adipocytes. These cells also exhibited an increased sensitivity to inhibition by the adenosine agonist, N6-(L-2-phenylisopropyl)-adenosine, either in combination with forskolin or beta-adrenergic hormone stimulation. Treatment of isolated adipocytes with pertussis toxin, which uncouples receptor-mediated Gi function, had little effect in cells from lean rats but increased isoproterenol stimulated cAMP production of cells from obese rats to levels observed in the lean cells. In addition, the adenosine A1 antagonist, 8-phenyltheophylline, increased cAMP and lipolytic activity in the obese adipocytes while having little significant effect in the lean adipocytes. These results suggest that hormonal control of lipolysis is altered in the obese Zucker rat because of an alteration in A1-adenosine receptor-mediated inhibition of adenylate cyclase.
...
PMID:A1-adenosine receptor-mediated inhibition of adipocyte adenylate cyclase and lipolysis in Zucker rats. 255 74

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.
...
PMID:Rapid enhancement of cAMP accumulation in rat brain particulate fraction after ischaemia. 255 46

The potent inhibitor of platelet cAMP phosphodiesterase (PDE) HL 725 (9,10-Dimethoxy-2-mesitylimino-3-methyl-3, 4,6,7-tetrahydro-2H-pyrimido(6,1-A)-isoquinoline-4-one-hydrochloride), was examined for its effects on human and rat platelet aggregation. Strong inhibitory effects are seen on collagen-induced platelet aggregation both in rat platelet-rich plasma (PRP) (IC50, 54 +/- 12 nM) and whole blood (IC50, 57 +/- 25 nM). Compared to the effects on rat platelets, HL 725 is about two-fold less inhibitory in human PRP (IC50, 94 +/- 29 nM) and whole blood (IC50, 126 +/- 50 nM). The inhibitory action of HL 725 can be reversed by washing and resuspension of the platelets, suggesting that HL 725 does not bind tightly to cAMP PDE. If human or rat PRP is pretreated with adenosine deaminase, an enzyme that degrades adenosine or 2',5'-dideoxyadenosine, an inhibitor of adenylate cyclase, the inhibitory effect of HL 725 is reversed. Similar blockade of the inhibitory actions of several other inhibitors of cAMP PDE such as RA 233, RX-RA 69 (analogs of dipyridamole) and oxagrelate is seen by adenosine deaminase pretreatment. The nucleoside transport inhibitors, dilazep and dipyridamole which are non-inhibitory alone to platelet aggregation, strongly potentiate (about 10-fold) the inhibitory action of HL 725 on collagen-induced platelet aggregation in human whole blood. However, if the whole blood is pretreated with adenosine deaminase, no inhibitory effect of dipyridamole plus HL 725 is seen on platelet aggregation. These studies demonstrate that plasma adenosine plays a crucial role in the antiaggregatory actions of HL 725 and several other inhibitors of cAMP PDE both in human and rat blood.
...
PMID:Role of plasma adenosine in the antiplatelet action of HL 725, a potent inhibitor of cAMP phosphodiesterase: species differences. 282 50

Sertoli cells cultured from immature hamsters respond to FSH with a dose-related increase in cAMP accumulation. Pertussis toxin acts synergistically with FSH to stimulate cAMP accumulation. This effect of pertussis toxin indicates that Sertoli cell adenylate cyclase is under tonic inhibition due to the activity of the Ni inhibitory transducer. The acetylcholine receptor antagonists atropine or tubocurarine, or the opioid antagonist naltrexone, have no effect on the FSH-induced stimulation of cAMP accumulation, suggesting that neither acetylcholine nor opioids are responsible for the inhibition of Sertoli cell cyclase. While exogenous adenosine is inhibitory, adenosine deaminase augments the ability of FSH to stimulate cAMP accumulation, but not to the level of pertussis toxin. This indicates that the Sertoli cells produce endogenous adenosine that is at least partially responsible for the tonic inhibition of adenylate cyclase. Other possibilities for the tonic inhibition of cyclase include other Sertoli cell products, germ cell products, peritubular cell products or an action of FSH itself through both stimulatory and inhibitory transducers.
...
PMID:Tonic inhibition of adenylate cyclase in cultured hamster Sertoli cells. 282 41

The specific activities of adenosine deaminase (ADA) in 16 murine tumor cell lines derived from seven UV light-induced neoplasms (melanoma and fibrosarcoma) were determined. In each case, the specific activity of ADA correlated positively with the antigenicity of the tumor cells. Highly antigenic cell lines that regress upon introduction into syngeneic hosts had on average 4- to 6-fold higher ADA specific activities than cell lines of low antigenicity that grow progressively in syngeneic hosts. The antigenic differences are probably not related to intracellular cAMP levels, as the level of cAMP differed only 2-fold between the two groups of cell lines.
...
PMID:Antigenicity of UV radiation-induced murine tumors correlates positively with the level of adenosine deaminase activity. 282 50

Isolated metabolically stable cardiomyocytes from adult rats and mongrel dogs were used to characterize the mechanism underlying the antiadrenergic effect of adenosine. In a system not affected by cellular heterogeneity, isoproterenol (3 x 10(-9) M - 10(-5) M) in the presence of adenosine deaminase (5U/ml) dose dependently increased cellular cAMP (5-80 pmol/mg). The effect of isoproterenol (0.1 microM) was inhibited by various adenosine derivatives, the rank order of potency being in the rat: (-)-N6-(R-phenyl-isopropyl)-adenosine (R-PIA) greater than 5'-N-ethylcarboxamidoadenosine (NECA) greater than S-PIA, and in the dog NECA greater than R-PIA greater than S-PIA. The cAMP increase induced by forskolin (1 microM) was attenuated in the rat by R-PIA. 8-phenyltheophylline (3 microM) antagonized the effect of R-PIA on isoproterenol-stimulated cAMP formation. Basal cAMP content was not influenced by R-PIA or NECA. Omission of adenosine deaminase from the incubation medium attenuated the isoproterenol-induced cAMP increase in the rat by about 30%. Our findings provide evidence for the presence of adenylate cyclase-coupled A1-adenosine receptors on cardiomyocytes which may mediate the antiadrenergic effect of adenosine in the heart.
...
PMID:Evidence for adenylate cyclase-coupled A1-adenosine receptors on ventricular cardiomyocytes from adult rat and dog heart. 282 51

The histamine-stimulated accumulation of [3H]cAMP (formed by prelabeling with [3H]adenine) was characterized pharmacologically in a vesicular preparation of guinea pig cortex. The H2 antagonist cimetidine maximally blocked 80% of the response, whereas only 45% of the response could be inhibited by H1 antagonists. A combination of H1 and H2 antagonists completely abolished the response. These and other findings show that both H1 and H2 receptors mediate the response, but 25% of the response may require simultaneous activation of both receptors. A role for adenosine as a mediator of the histamine response was investigated. Adenosine deaminase (EC 3.5.4.4., 2.5 units/ml) decreased basal [3H]cAMP levels, abolished the cimetidine-resistant component of the histamine response, and reduced maximal H1 antagonism of the histamine response to 30%. Treatment with a combination of adenosine deaminase and the calcium chelator EGTA (2 mM) appeared to eliminate the H1 component completely. Under these latter conditions only H2 receptors appeared to mediate the histamine response. Thus, both H1 and H2 receptors stimulate [3H]cAMP accumulation in the vesicular preparation, but the H1 response seems to require either concomitant adenosine or H2 receptor stimulation and may be calcium dependent. These findings differ from those found in broken cell membrane preparations, where only H2 receptors appear to be coupled to adenylate cyclase activation.
...
PMID:Histamine receptors coupled to [3H]cAMP accumulation in brain: pharmacological characterization in a vesicular preparation of guinea pig cortex. 282 98

There is evidence that phosphatidylcholine secretion in type II pneumocytes is stimulated by adenosine and adenine nucleotides and that the effect of adenosine is mediated by the A2 subtype of the P1 purinoceptor. To determine if the effect of ATP is also mediated by the same receptor following its catabolism to adenosine or by the P2 purinoceptor we compared the effects of adenosine and ATP. Adenosine and terbutaline stimulated phosphatidylcholine secretion approx. 2-fold, while ATP stimulated it by more than 3-fold, essentially to the same extent as the protein kinase C activator, 12-O-tetradecanoylphorbol 13-acetate. The stimulatory effect of adenosine but not of ATP was abolished by adenosine deaminase. The effect of ATP was markedly diminished by the P2 desensitizing agent alpha,beta-methylene ATP, but only slightly by the P1 antagonist 8-phenyltheophylline. Adenosine increased the cAMP content of type II cells while ATP had little effect. The effects of ATP and terbutaline were additive while those of adenosine and terbutaline were not. These data show that ATP and adenosine stimulate phosphatidylcholine secretion via different mechanisms. Therefore, the effect of ATP is not mediated via catabolism to adenosine. Metabolically resistant analogs of ATP also stimulated secretion in a concentration-dependent manner although none were as potent as ATP. The order of potency was ATP greater than beta,gamma-methylene ATP = 2-methylthio ATP = 2-deoxy ATP greater than or equal to 8-bromo ATP greater than alpha,beta-methylene ATP. The facts that ATP analogs also stimulate secretion and that the effect of ATP was antagonized by alpha,beta-methylene ATP suggest that the stimulatory effect of ATP is mediated by the P2 purinoceptor.
...
PMID:Functional evidence for involvement of P2 purinoceptors in the ATP stimulation of phosphatidylcholine secretion in type II alveolar epithelial cells. 283 Sep 2

Adenosine produced a slight but concentration-dependent relaxation in rabbit aortic strips preconstricted with norepinephrine. The effect of adenosine was markedly augmented in the presence of hydralazine. On the other hand, the adenosine-induced relaxation was attenuated by 8-phenyltheophylline, but was unaffected by indomethacin, nordihydroguaiaretic acid and quinacrine, indicating that adenosine acts via purinergic receptors and that vasodilating metabolites of arachidonic acid are not involved in the relaxation. The adenosine-induced relaxation remained unaffected by S-(p-nitrobenzyl)-6-thioguanosine (NBTG) or 2'-deoxycoformycin (2'DCF), alone or combined. NBTG significantly inhibited the incorporation of [3H] adenosine, while the content of [3H] compound was increased by 2'DCF, but was unchanged by hydralazine. Hydralazine also augmented the 2-chloroadenosine-induced relaxation. These results suggest that the augmentation of adenosine-induced relaxation with hydralazine does not result from an inhibition of adenosine transport and/or adenosine deaminase. When adenosine was added, relaxation was elicited with concomitant increase in cAMP, but with no significant change in cGMP. In the presence of hydralazine, the cAMP increasing effect of adenosine was augmented, and the level of cGMP increased with adenosine. These changes in cyclic nucleotide levels might at least in part explain the augmentation of adenosine-induced relaxation with hydralazine.
...
PMID:Augmentation of adenosine-induced relaxation response with hydralazine in aortic strips. 283 34


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---