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

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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)

The purpose of the present study was to examine mechanisms of activity-dependent changes of cerebral blood flow (CBF) in rat cerebellar cortex by laser-Doppler flowmetry, using two synaptic inputs that excite different regions of the same target cell and with different synaptic strength. The apical part of Purkinje cells was activated by electrical stimulation of parallel fibers, whereas the cell soma and the proximal part of the dendritic tree were activated by climbing fibers using harmaline (40 mg/kg ip) or electrical stimulation of the inferior olive. Glass microelectrodes were used for recordings of field potentials and single-unit activity of Purkinje cells. CBF increases evoked by parallel fibers were most pronounced in the upper cortical layers. In contrast, climbing fiber stimulation increased CBF in the entire cortex. Inhibition of nitric oxide (NO) synthase activity by NG-nitro-L-arginine (L-NNA) or guanylate cyclase activity by 1H-[1,2,4(oxadiazolo)4,3-a]quinoxaline-1-one did not affect basal or harmaline-induced Purkinje cell activity but attenuated harmaline- and parallel fiber-evoked CBF increases by approximately 40-50%. Application of 8-(p-sulfophenyl)theophylline and adenosine deaminase reduced the harmaline-evoked CBF increase without any effect on the parallel fiber-evoked CBF response. The results suggest that CBF increases elicited by activation of Purkinje cells are partially mediated by the NO-guanosine 3',5'-cyclic monophosphate system independent of the input function but that adenosine contributes as well when climbing fibers are activated. This is the first demonstration of variations of coupling as a function of postsynaptic activity in the same cell.
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PMID:Laminar analysis of activity-dependent increases of CBF in rat cerebellar cortex: dependence on synaptic strength. 932 3

Although infectious, inflammatory and neoplastic diseases frequently involve the pleural space and walls, little is known about the immunological and molecular mechanisms underlying pleural disorders. This article provides an overview of recent insights into immunobiological processes likely to play a role in the pathogenesis of pleural disorders. Pleural involvement in certain diseases is associated with the infiltration of a number of different types of immune cells, such as neutrophils, eosinophils or lymphocytes, in various proportions depending on both the course and the aetiology of the underlying disease. In addition to infiltrating cells, mesothelial cells have been demonstrated to actively participate in pleural inflammation via release of various mediators and proteins, including platelet-derived growth factor (PDGF), interleukin-8, monocyte chemotactic peptide (MCP-1), nitric oxide (NO), collagen, antioxidant enzymes and the plasminogen activation inhibitor (PAI). Furthermore, several inflammatory mediators have been detected at increased concentrations within pleural effusions, including lipid mediators, cytokines and proteins (adenosine deaminase, lysosyme, eosinophil-derived cationic proteins, and products of the coagulation cascade). The presence of these mediators underline the concept of pleural inflammation, and certain cytokines seem to characterize a specific aetiology of pleurisy. The understanding of these processes and the sequence of events leading to pleural loculation, pleural adhesion or repair are likely to provide the basis for early therapeutic intervention and reduce pleural-associated morbidity.
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PMID:Immunobiology of pleural inflammation: potential implications for pathogenesis, diagnosis and therapy. 938 73

The present study has employed immunocytochemistry on free-floating sections of adult rat medulla oblongata to characterise the distribution of nitric oxide synthase- (NOS), adenosine deaminase- (ADA) and neuropeptide Y- (NPY) immunoreactivity (IR) throughout the entire rostro-caudal axis of the nucleus tractus solitarius (NTS). In addition, unilateral nodose ganglionectomy was performed in a group of rats to determine whether any observed immunoreactivity was associated with central vagal afferent terminals. NOS-IR was found throughout the entire NTS, in cells, and both varicose and non-varicose fibres. Furthermore, unilateral nodose ganglionectomy resulted in a clear reduction in NOS-IR (visualised with diaminobenzidine) in a highly restricted portion of the ipsilateral medial NTS. Similarly, ADA- and NPY-containing cells, fibres and terminals were also found throughout the adult rat NTS. However, following unilateral nodose ganglionectomy, there was no apparent reduction in either ADA-IR or NPY-IR on the denervated side of the NTS. These data indicate a role for nitric oxide, purines and neuropeptide Y as neuromodulators within the rat NTS, although only nitric oxide appears to be primarily associated with vagal afferent input. Adenosine deaminase and neuropeptide Y-containing neurons appear to be predominantly postsynaptic to vagal input, although their possible association with vagal afferents cannot be completely excluded.
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PMID:The distribution of nitric oxide synthase-, adenosine deaminase- and neuropeptide Y-immunoreactivity through the entire rat nucleus tractus solitarius: Effect of unilateral nodose ganglionectomy. 971 Jan 47

In the present investigation, effect of rat peripheral polymorphonuclear leukocyte (PMNL) supernatant was investigated on platelet aggregation. Rat PMNLs suspended in Hanks balanced salt solution (HBSS, pH 7.4) were incubated at 37 degrees C for different time intervals and cell-free supernatant was obtained by centrifugation. Supernatant was found to inhibit adenosine diphosphate (ADP), arachidonic acid (AA), and calcium ionophore-induced platelet aggregation. The inhibitory effect of PMNL supernatant on platelet aggregation was not blocked by methylene blue (10 microM) or adenosine deaminase (5 U ml(-1)) pretreatment, suggesting that the inhibitory effect of the supernatant on aggregation was not mediated by nitric oxide (NO) or ecto-ADPase. The effect of PMNL supernatant on platelet aggregation was abolished by preheating the supernatant at 95 degrees C for 5 minutes. Pretreatment of the supernatant with protease inhibitors abolished the inhibitory effect of supernatant on platelet aggregation suggesting that the factor may be a protein or peptide with protease activity. Partial purification of biologically active factor by fine particle liquid chromatography (FPLC) by using Superose 6B column yielded a peak with a molecular weight of approximately 30 kDa having antiaggregatory activity. The results obtained suggest that rat peripheral PMNLs release yet another factor(s) that inhibits platelet aggregation. The factor is a heat labile protein with a molecular weight of approximately 30 kDa.
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PMID:Inhibition of platelet aggregation by a protein factor present in rat peripheral polymorphonuclear leukocyte supernatant. 972 23

The vasoactive substances adenosine and nitric oxide (NO) are credible candidates in the local regulation of skeletal muscle blood flow. Adenosine and NO have both been shown to increase in skeletal muscle cells and interstitial fluid during exercise and the enzymes responsible for their formation, AMP 5'-nucleotidase and NO synthase (NOS), have been shown to be activated upon muscle contraction. In vitro as well as in vivo evidence suggest that the contraction-induced increase in interstitial adenosine concentration largely stems from extracellular formation via the membrane-bound ecto-form of AMP 5'-nucleotidase. It remains unclear whether the exercise-induced NO formation in muscle originates from endothelial NOS in the microvascular endothelium, or from neuronal NOS (nNOS) in nerve cells and muscle fibres. Functional evidence for the role of adenosine in muscle blood flow control stems from studies using adenosine receptor agonists and antagonists, adenosine deaminase or adenosine uptake inhibitors. The majority of these studies have been performed on laboratory animals and, although the results show some discrepancy, the majority of studies indicate that adenosine does participate in the regulation of muscle blood flow. In humans, evidence is lacking. The role of NO in the regulation of skeletal muscle blood flow has mainly been studied using NOS inhibitors. Despite a large number of studies in this area, the role of NO for the contraction-induced increase in skeletal muscle blood flow is uncertain. The majority, but not all, human and animal studies show that, whereas blockade of NOS reduces muscle blood flow at rest and in recovery from exercise, there is no effect on the exercise-induced increase in muscle perfusion. Conclusive evidence for the mechanisms underlying the precise regulation of the multiphased increase in skeletal muscle blood flow during exercise and the role and potency of various vasoactive substances, remain missing.
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PMID:Adenosine and nitric oxide in exercise-induced human skeletal muscle vasodilatation. 1075 94

Stimulation of N-methyl-D-aspartate (NMDA) receptors on neurons activates both cAMP and cGMP signaling pathways. Experiments were carried out to determine which phosphodiesterase (PDE) families are involved in the hydrolysis of the cyclic nucleotides formed via this mechanism, using primary neuronal cultures prepared from rat cerebral cortex and hippocampus. The nonselective PDE inhibitor 3-isobutyl-1-methylxanthine (IBMX) potentiated the ability of NMDA to increase cAMP and cGMP. However, among the family-selective inhibitors, only the PDE4 inhibitor rolipram enhanced the ability of NMDA to increase cAMP in the neurons. In contrast, only the PDE2 inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) enhanced the ability of NMDA to increase cGMP. Neither adenosine nor an adenosine deaminase inhibitor mimicked the effect of EHNA; this suggests that EHNA's inhibition of PDE2, not its effects on adenosine metabolism, mediates its effects on NMDA-stimulated cGMP concentrations. The PDE inhibitor-augmented effects of NMDA on cAMP and cGMP formation were antagonized by 5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine maleate (MK-801), verifying NMDA receptor mediation. In contrast, only NMDA-mediated cGMP formation was affected by altering either nitric oxide signaling or guanylyl cyclase; this suggests that NMDA-induced changes in cAMP are not secondary to altered cGMP concentrations. Overall, the present findings indicate that cAMP and cGMP formed in neurons as a result of NMDA receptor stimulation are hydrolyzed by PDE4 and PDE2, respectively. Selective inhibitors of the two PDE families will differentially affect the functional consequences of activation of these two signaling pathways by NMDA receptor stimulation.
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PMID:Hydrolysis of N-methyl-D-aspartate receptor-stimulated cAMP and cGMP by PDE4 and PDE2 phosphodiesterases in primary neuronal cultures of rat cerebral cortex and hippocampus. 1206 24

Long-term ethanol consumption at low to moderate levels exerts cardioprotective effects in the setting of ischemia and reperfusion (I/R). The aims of this study were to determine whether 1) a single orally administered dose of ethanol [ethanol preconditioning (EtOH-PC)] would induce a biphasic temporal pattern of protection (early and late phases) against the inflammatory responses to I/R and 2) adenosine and nitric oxide (NO) act as initiators of the late phase of protection. Ethanol was administered as a bolus to C57BL/6 mice at a dose that achieved a peak plasma concentration of ~45 mg/dl 30 min after gavage and returned to control levels within 60 min of alcohol ingestion. The superior mesenteric artery was occluded for 45 min followed by 60 min of reperfusion beginning 10 min or 1, 2, 3, 4, or 24 h after ethanol ingestion, and the numbers of fluorescently labeled rolling and firmly adherent (stationary) leukocytes in single postcapillary venules of the small intestine were quantified using intravital microscopic approaches. I/R induced marked increases in leukocyte rolling and adhesion, effects that were attenuated by EtOH-PC 2-3 h before I/R (early phase), absent when assessed after 10 min, 1 h, and 4 h of ethanol ingestion, with an even more powerful late phase of protection reemerging when I/R was induced 24 h later. The anti-inflammatory effects of late EtOH-PC were abolished by treatment with adenosine deaminase, an adenosine A(2) (but not A(1)) receptor antagonist, or a NO synthase (NOS) inhibitor during the period of EtOH-PC. Preconditioning with an adenosine A(2) (but not an A(1)) receptor agonist in lieu of ethanol 24 h before I/R mimicked the protective actions of late phase EtOH-PC. Like EtOH-PC, the effect of preconditioning with an adenosine A(2) receptor agonist was abrogated by coincident NOS inhibition. These findings suggest that EtOH-PC induces a biphasic temporal pattern of protection against the proinflammatory effects of I/R. In addition, our observations are consistent with the hypothesis that the late phase of EtOH-PC is triggered by NO formed secondary to adenosine A(2) receptor-dependent activation of NOS during the period of ethanol exposure.
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PMID:Preconditioning with ethanol prevents postischemic leukocyte-endothelial cell adhesive interactions. 1218 Nov 32

The aim of this experimental study was to investigate the effects of erdosteine, an antioxidant agent, on doxorubicin (DXR)-induced cardio-toxicity through nitric oxide (NO) levels, collagen synthesis, xanthine oxidase (XO) and adenosine deaminase (ADA) activities in rats. Rats were treated with erdosteine (10 mg/kg b.wt. per day, orally) or saline starting 2 days before administrating a single dose of DXR (20 mg/kg i.p.) or saline. At the 10th day of the DXR administration, hearts were removed under anesthesia for biochemical measurements. Enzyme activities as well as OH-proline and NO levels were found to be significantly increased in DXR group compared with the control group. All of the parameters studied except ADA activity were decreased significantly approximating to the control levels upon erdosteine administration. In conclusion, erdosteine seems to be an alternative agent for protection of cardiac tissue against DXR-induced cardio-toxicity through its regulatory effect on XO activity and NO level.
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PMID:The activities of tissue xanthine oxidase and adenosine deaminase and the levels of hydroxyproline and nitric oxide in rat hearts subjected to doxorubicin: protective effect of erdosteine. 1296 18

We have previously reported that, depending on the dose, nitric oxide (NO)-generating agents exert a dual facilitatory and inhibitory action on glutamatergic transmission on the rostral ventrolateral medulla (RVLM) neurons. The molecular mechanisms underlying the NO-mediated synaptic inhibition have not yet been defined. Here we show that the amplitude of excitatory postsynaptic currents (EPSCs) was reversibly reduced by the NO donors 3-morpholinylsydnoneimine (SIN-1) (1 mM) and spermine NONOate (1 mM). This effect was antagonized by an active peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(4-sulfonatophenyl)prophyrinato iron (III) chloride, G(i/o)-coupled receptor blockers, N-ethylmaleimide and pertussis toxin, A(1) adenosine receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine, or adenosine deaminase. However, NO-sensitive guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, GABA(B) receptor antagonist (2S)-(+)-5,5-dimethyl-2-morpholineacetic acid (SCH50911), or cannabinoid receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride (SR141716A) had no effect on the inhibitory action of SIN-1 on EPSCs. Perfusion of adenosine mimicked and subsequently occluded the action of SIN-1. Inhibition of EPSC amplitude by SIN-1 was associated with an increase in the paired-pulse ratio of EPSCs. Furthermore, SIN reduced the frequency of spontaneous EPSCs without altering their amplitude of distribution. Pretreatment with N-type Ca(2+)-channel blocker omega-conotoxin GVIA selectively blocked SIN-1-induced inhibition of EPSCs. These results suggest that a higher dose of SIN-1 acts presynaptically to elicit a synaptic depression on the RVLM neurons through an inhibition of presynaptic N-type Ca(2+)-channel activity, leading to reduced glutamate release. The presynaptic action of SIN-1 is mediated by the formation of peroxynitrite, which subsequently acts to release adenosine to activate A(1) adenosine receptors.
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PMID:3-Morpholinylsydnonimine inhibits glutamatergic transmission in rat rostral ventrolateral medulla via peroxynitrite formation and adenosine release. 1532 40

The aim of this experimental study was to investigate whether nebivolol has protective effects against neuronal damage induced by spinal cord ischemia/reperfusion (I/R). Twenty-one rabbits were divided into three groups: group I (control, no I/R), group II (only I/R) and group III (I/R+nebivolol). Spinal cord ischemia was induced by clamping the aorta both below the left renal artery and above the aortic bifurcation. Seventy-two hours postoperatively, the motor function of the lower limbs was evaluated in each animal. The animals were sacrificed at 72 h, and histopathological and biochemical analyses were carried out in the lumbar spinal cords. The motor deficit scores in nebivolol group were different from I/R group at 72 h (3.25+/-0.70 vs. 1.75+/-1.28, p=0.01). I/R produced a significant increase in the superoxide dismutase (SOD), xanthine oxidase (XO), adenosine deaminase (ADA) and myeloperoxidase (MPO) activities in spinal cord tissue when compared with control group. Nebivolol treatment prevented the increase of all those enzymes activities produced by I/R. A significant decrease in spinal cord glutathione peroxidase (GSH-Px) level was seen in I/R group and nebivolol treatment prevented the decrement in the spinal cord tissue GSH-Px contents. On the other hand, I/R produced a significant increase in the spinal cord tissue malondialdehyde (MDA) and nitric oxide (NO) contents, this was prevented by nebivolol treatment. In conclusion, this study demonstrates a considerable neuroprotective effect of nebivolol on neurological, biochemical and histopathological status during periods of spinal cord I/R in rabbits.
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PMID:The protective effect of nebivolol on ischemia/reperfusion injury in rabbit spinal cord. 1561 Sep 28


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