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)

1. Glutamate inhibits the electrically evoked release of noradrenaline in rabbit brain cortex slices; the inhibition is mediated by adenyl compounds, presumably adenosine. The aim of the present study was to identify the receptors involved in this indirect inhibitory effect of glutamate. Slices of the occipitoparietal cortex were preincubated with [3H]-noradrenaline and then superfused and stimulated by trains of 6 pulses, 100 Hz. 2. The ionotropic glutamate receptor agonists alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AM-PA; 10-100 microM), kainate (10-100 microM) and N-methyl-D-aspartate (NMDA; 30-300 microM) but not the metabotropic glutamate receptor agonist, 1-amino-1,3-cyclopentanedicarboxylate (ACPD; 10-100 microM) reduced the electrically evoked overflow of tritium. 3. The effects of AMPA, kainate and NMDA were attenuated or abolished by the adenosine A1-receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) as well as by adenosine A1-receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) as well as by adenosine deaminase but not by the alpha 2-adrenoceptor antagonist yohimbine, the gamma-aminobutyric acid (GABA) receptor antagonists, bicuculline and 2-hydroxysaclofen and the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). 4. The NMDA receptor antagonist, 2-amino-5-phosphonopentanoate (AP5) blocked the inhibitory effect of NMDA but not that of AMPA and kainate. The non-NMDA-receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) blocked the effect of AMPA but not of kainate and NMDA. 5. In addition to decreasing the electrically evoked overflow of tritium, AMPA, kainate and NMDA but not ACPD caused a steep but transient rise of basal tritium efflux. This immediate releasing effect was not significantly changed by DPCPX, adenosine deaminase, yohimbine, bicuculline, 2-hydroxysaclofen and L-NAME (except that L-NAME enhanced the effect of kainate). AP5 and CNQX antagonized the immediate releasing effects in the same way that they antagonized the inhibition by AMPA, kainate and NMDA of the electrically evoked overflow of tritium.6. It is concluded that AMPA, kainate and NMDA, like glutamate, reduce the electrically evoked release of noradrenaline by releasing adenosine or an adenine nucleotide which is then degraded to adenosine. Activation of each of the three ionotropic glutamate receptors, AMPA, kainate and NMDA receptors, but not activation of metabotropic glutamate receptors can initiate this indirect inhibitory effect on the release of noradrenaline (as well as the known noradrenaline releasing effect).
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PMID:Ionotropic glutamate receptor types leading to adenosine-mediated inhibition of electrically evoked [3H]-noradrenaline release in rabbit brain cortex slices. 750 27

KCl-evoked glutamate exocytosis from cerebrocortical synaptosomes can be inhibited by the adenosine A1 receptor agonist cyclohexyladenosine (CHA). Inhibition is associated with a decreased KCl-evoked Ca2+ level elevation, and the effect of the agonist is occluded by prior incubation with the Agelenopsis aperta neurotoxin omega-agatoxin-IVA at 250 nM. The inhibition is suppressed in the presence of 3 nM phorbol dibutyrate (PDBu) or by activation of the protein kinase C (PKC)-coupled metabotropic glutamate receptor by 100 microM (1S,3R)-1-aminocyclopentane-1,3-dicarboxylate [(1S,3R)ACPD]. A tonic inhibition of release by leaked exogenous adenosine can be reversed by adenosine deaminase or by PDBu addition. The CHA-induced inhibition can be enhanced by the PKC inhibitor Ro 31-8220. The mechanism for the suppression of the adenosine A1 receptor-mediated inhibition is distinct from that previously described for the (1S,3R)ACPD-evoked, PKC-mediated, facilitatory pathway, which enhances phosphorylation of the MARCKS protein, 4-aminopyridine-induced action potentials, and release of glutamate because the latter requires at least 100 nM PDBu [or the combination of (1S,3R)ACPD and arachidonic acid] and is not seen following KCl depolarization. Both PKC-mediated pathways may be involved in the presynaptic events associated with the establishment of synaptic plasticity.
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PMID:Protein kinase C-mediated suppression of the presynaptic adenosine A1 receptor by a facilitatory metabotropic glutamate receptor. 761 16

Adenosine 3',5'-cyclic monophosphate (cAMP), accumulated in the presence of adenosine, was measured in medullary portions of mouse thick ascending limbs of Henle's loop, suspended either in classic extracellular buffer or in the presence of added NaCl. Under control conditions (140 mmol/l NaCl), adenosine (< 10(-5) mol/l) and N6-cyclohexyladenosine, an A1 adenosine receptor agonist, inhibit the cAMP accumulation induced by arginine vasopressin (AVP). On the other hand, high concentrations of adenosine and CGS-21680, an A2 adenosine receptor agonist, stimulate cAMP formation. Addition of NaCl (+300 mmol/l) to extracellular buffer stimulates the release of endogenous adenosine. It also enhances A2 receptor-induced cAMP accumulation but suppresses A1 receptor-mediated inhibition of adenylyl cyclase. This hypertonic NaCl medium also potentiates the stimulatory action of AVP on adenylyl cyclase. The modifications of tubular responses to both AVP and A1 and A2 agonists, brought about by hypertonic NaCl, were all inhibited by adenosine deaminase, thereby demonstrating the involvement of endogenous adenosine. Adenosine, the release and the effects of which are modulated by hypertonic NaCl, thus appears to act as an endogenous physiological modulator of kidney medulla function.
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PMID:Hypertonic NaCl enhances adenosine release and hormonal cAMP production in mouse thick ascending limb. 763 23

The influence of the activation of presynaptic adenosine receptors on nicotinic autofacilitation of electrically evoked [3H]acetylcholine release from rat phrenic motor nerve terminals was investigated. Blocking the adenosine A2A receptor with 3,7-dimethyl-1-propargylxanthine (DMPX, 10 microM) greatly potentiated, whereas the adenosine A1 receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 2.5 nM), partially prevented the facilitatory effect of the nicotinic receptor agonist, 1,1-dimethyl-4-phenylpiperazinium (DMPP, 1 microM, 3 min), on evoked [3H]acetylcholine release. The adenosine A2A receptor agonist, 2-[p-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamideadeno sine (CGS 21680C, 3 nM), but not the adenosine A1 receptor agonist, R-N6-phenylisopropyl adenosine (R-PIA, 300 nM), partially blocked the DMPP (1 microM) facilitation. Forskolin (3 microM) mimicked the attenuation caused by CGS 21680C; inhibition of adenylate cyclase with N-(as-2-phenylcyclopentyl)azacyclo-tridecan-2-imine hydrochloride (MDL 12,330A, 10 microM) markedly enhanced the facilitatory effect of DMPP (1 microM). Prolonged exposure to a high concentration of DMPP (10 microM, 15 min) decreased evoked tritium outflow. The decrease in evoked [3H]acetylcholine release following prolonged exposure to DMPP was augmented by pretreatment with CGS 21680C (3 nM) and forskolin (3 microM), and was abolished by inactivating endogenous adenosine with adenosine deaminase (0.5 U/ml). It is concluded that tonic adenosine A2A receptor activation regulates nicotinic acetylcholine autofacilitation. This action is likely to be mediated through an adenylate cyclase/cyclic AMP-dependent mechanism.
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PMID:Tonic adenosine A2A receptor activation modulates nicotinic autoreceptor function at the rat neuromuscular junction. 770 35

Brief exposure of primary cultures of hepatocytes to ethanol had a biphasic effect on glucagon receptor-dependent cyclic AMP (cAMP) production: 25-50 mM ethanol decreased cAMP levels, whereas treatment with 100-200 mM ethanol increased cAMP. This biphasic effect was also observed after pretreatment with 10 microM 4-methylpyrazole, an inhibitor of alcohol dehydrogenase. Adenosine A1 and A2 receptors in primary cultures of rat hepatocytes are coupled to inhibition and stimulation of adenylyl cyclase, respectively. Since primary cultures of hepatocytes release adenosine into their extracellular media, we tested whether the acute effects of ethanol on cAMP were mediated by extracellular adenosine. Co-incubation with 2 U/mL adenosine deaminase prevented inhibition of cAMP production by 25-50 mM ethanol, but had no effect on stimulation by 100-200 mM ethanol. Pretreatment of hepatocytes with 110 nM 8-cyclopentyl-1,3-dimethylxanthine, an adenosine A1 receptor antagonist, also completely blocked the inhibitory effects of ethanol on cAMP production. Low concentrations of ethanol enhanced the inhibitory effects of R(-)N6-(2-phenylisopropyl)adenosine, an A1 receptor agonist, on cAMP production in cells pretreated with adenosine deaminase to remove endogenous adenosine. These data suggest that endogenously produced adenosine can be an important modulator of the effects of ethanol on receptor-stimulated cAMP production in primary cultures of rat hepatocytes.
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PMID:Role of adenosine A1 receptors in inhibition of receptor-stimulated cyclic AMP production by ethanol in hepatocytes. 780 99

Cellular responses to adenosine depend on the distribution of the two adenosine receptor subclasses. In primary cultures of rat hepatocytes, adenosine receptors were coupled to adenylate cyclase via A1 and A2 receptors which inhibit and stimulate cyclic AMP production respectively. R-(-)-N6-(2-phenylisopropyl)-adenosine (R-PIA), the adenosine A1 receptor-selective agonist, inhibited glucagon-stimulated cyclic AMP production with an IC50 of 19 nM. This inhibition was blocked by the A1-specific antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPDX). 5'-N- Ethylcarboxamidoadenosine (NECA), an agonist which stimulates A2 receptors, increased cyclic AMP production with an EC50 of 0.6 microM. Treatment of primary cultures of rat hepatocytes with 100 mM ethanol for 48 h decreases the quantity and function of the inhibitory guanine-nucleotide regulatory protein (G(i)), resulting in a sensitization of receptor-stimulated cyclic AMP production [Nagy and deSilva (1992) Biochem. J. 286, 681-686]. When cells were cultured with 2 units/ml adenosine deaminase, to degrade extracellular adenosine, ethanol-induced increases in cyclic AMP production were completely prevented. Moreover, the specific A1-receptor antagonist, CPDX, also blocked the chronic effects of ethanol on receptor-stimulated cyclic AMP production. Treatment with adenosine deaminase or CPDX also prevented the decrease in quantity of the alpha subunit protein of G(i) observed in hepatocytes after chronic treatment with ethanol. Taken together, these results suggest that activation of adenosine A1 receptors on primary cultures of hepatocytes is involved in the development of chronic ethanol-induced sensitization of receptor-stimulated cyclic AMP production.
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PMID:Adenosine A1 receptors mediate chronic ethanol-induced increases in receptor-stimulated cyclic AMP in cultured hepatocytes. 799 34

The adenosine modulation of glutamate exocytosis from guinea pig cerebrocortical synaptosomes is investigated. Endogenously leaked adenosine is sufficient to cause a partial tonic inhibition of 4-aminopyridine-evoked glutamate release, which can be relieved by adenosine deaminase. The adenosine A1 receptor is equally effective in mediating inhibition of glutamate exocytosis evoked by 4-aminopyridine (where K(+)-channel activation would inhibit release) and by elevated KCl (where K(+)-channel activation would have no effect), arguing for a central role of Ca(2+)-channel modulation. In support of this, the plateau phase of depolarization-evoked free Ca2+ elevation is decreased by adenosine with both depolarization protocols. No effect of adenosine agonists is seen on membrane potential in polarized or KCl- or 4-aminopyridine-stimulated synaptosomes. The interaction of protein kinase C with the A1 receptor-mediated inhibition is examined. Activation of protein kinase C by 4 beta-phorbol dibutyrate has been shown previously by this laboratory to modulate glutamate release via K(+)-channel inhibition, and is shown here to have an additional action of decoupling the adenosine inhibition of glutamate exocytosis.
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PMID:Adenosine A1 receptor inhibition of glutamate exocytosis and protein kinase C-mediated decoupling. 809 42

Modulation by exogenous and endogenous adenine nucleotides and adenosine of [3H]acetylcholine release evoked by veratridine (10 microM) was compared in synaptosomal fractions from the hippocampus and the cerebral cortex of the rat. In both brain areas, exogenously added ATP or adenosine (10-100 microM) inhibited the evoked tritium release. In the hippocampus, ATP gamma S, an ATP analogue more resistant to catabolism than ATP, was virtually devoid of effect on tritium release, and the effect of ATP was prevented by the ecto-5'-nucleotidase inhibitor alpha,beta-methylene ADP (100 microM), by adenosine deaminase (2 U/ml) and by the A1 adenosine receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 20 nM). In contrast, in the cerebral cortex, the effect of ATP on tritium release was not prevented by either alpha,beta-methylene ADP (100 microM) or adenosine deaminase (2 U/ml), and several ATP analogues (30 microM) inhibited release. The order of intensity of the inhibitory effects of the ATP analogues was: ATP gamma S > ATP > beta,gamma-imido ATP > beta,gamma-methylene ATP >> 2-methyl-S-ATP, alpha,beta-methylene ATP. The effect of ATP gamma S in the cerebral cortex was prevented by DPCPX (20 nM) and was not affected by the P2 purinoceptor antagonist suramin (100 microM). In the hippocampus, alpha,beta-methylene ADP (100 microM) increased the evoked release of tritium, and adenosine deaminase (2 U/ml) produced an even greater increase; when adenosine deaminase was added in the presence of alpha,beta-methylene ADP, adenosine deaminase still increased the evoked release of tritium. In the cerebral cortex, DPCPX (20 nM) and adenosine deaminase (2 U/ml) increased the evoked tritium release by a similar magnitude, but the effect of adenosine deaminase was smaller than in the hippocampus. It is concluded that in the cerebral cortex ATP as such presynaptically inhibits acetylcholine release, whereas in the hippocampus the role of adenine nucleotides is as a source of endogenous extracellular adenosine that tonically inhibits acetylcholine release. The results also show that besides formation of adenosine from adenine nucleotides, released adenosine as such contributes in nearly equal amounts to the pool of endogenous adenosine that presynaptically inhibits acetylcholine release in the hippocampus.
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PMID:Purinergic modulation of the evoked release of [3H]acetylcholine from the hippocampus and cerebral cortex of the rat: role of the ectonucleotidases. 813 Sep 31

The resting membrane potential of in vitro hamster diaphragm muscle fibers is depolarized on exposure to hypoxia. It was hypothesized that this depolarization was mediated by adenosine. It was predicted that the treatment of well-oxygenated hamster diaphragm muscle strips in vitro with adenosine or adenosine agonists would depolarize the diaphragm fiber membrane. Furthermore, resting membrane potential of hypoxic diaphragm fibers would be repolarized by (1) the removal of adenosine by the enzyme adenosine deaminase (ADA), or (2) the addition of an adenosine antagonist, BW A1433. Adenosine (10(-4) M) depolarized the membrane by 8 +/- 1 mV (p < 0.001). The adenosine agonist cyclopentyladenosine, which has predominantly A1 receptor affinity, depolarized the membrane from -75.4 +/- 5.6 mV to -68.9 +/- 5.7 mV (p < 0.001). The A2 adenosine receptor agonist 5'-N-ethylcarboxamide adenosine did not cause a significant depolarization. The addition of ADA (2 unit/ml) to hypoxic muscle returned the resting membrane potential to that of well-oxygenated fibers, p < 0.001 versus hypoxia. BW A1433 (3 x 10(-7)) also restored the membrane potential of hypoxic muscle fibers from -72 +/- 1 mV to -79 +/- 1 mV (p < 0.001). These observations suggest that adenosine via the A1 adenosine receptor mediates the hypoxic depolarization of in vitro hamster diaphragm muscle. A direct effect of adenosine on muscle membrane has not been described previously.
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PMID:Role of adenosine in the depolarization of hypoxic hamster diaphragm membrane in vitro. 814 55

We investigated the role of adenosine A1-receptor in the regulation of basolateral Na(+)-3HCO3- cotransporter in the rabbit proximal convoluted tubule (PCT) microperfused in vitro by monitoring basolateral membrane potential and intracellular pH. FK-453, a highly specific A1 antagonist, inhibited basolateral HCO3- conductance in a concentration-dependent manner (10(-10)-10(-5) M). Other A1 antagonists, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) at 10(-5) M and theophylline at 10(-3) M, also had similar effects. N6-cyclohexyladenosine (CHA) at 10(-7) M attenuated the effect of low concentration (10(-8) M) of FK-453. Either enhancement of the degradation of adenosine by 0.1 U/ml adenosine deaminase (ADA) or inhibition of adenosine release from the cells by 10(-6) M S-(4-nitrobenzyl)-6-thioinosine (NBTI) mimicked the effects of A1 antagonists. These observations suggest that endogenous adenosine is released from PCT cells and stimulates Na(+)-3HCO3- cotransporter. Both 10(-4) M 8-(4-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate (CPT-cAMP) and 10(-6) M forskolin also inhibited basolateral HCO3- conductance. Both 10(-6) M FK-453 and 10(-4) M CPT-cAMP decreased the initial rate as well as the magnitude of intracellular acidification induced by reduction of peritubular HCO3- concentration from 25 to 0 mM. Neither 10(-6) M FK-453 nor 10(-7) M CHA changed intracellular Ca2+ concentration as measured by fura-2 fluorescence. These results indicate that adenosine might stimulate HCO3- exit across the basolateral membrane through Na(+)-3HCO3- cotransporter by decreasing intracellular cAMP via A1-receptor activation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of Na(+)-3HCO3- cotransport in rabbit proximal convoluted tubule via adenosine A1 receptor. 823 80


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