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1.
ATP is an important excitatory neurotransmitter and adenosine acts as a neuromodulatory structure inhibiting neurotransmitters
release in the central nervous system. Since the ecto-nucleotidase cascade that hydrolyzes ATP to adenosine is involved in
the control of brain functions and previous studies realized in our laboratory have recently reported that acute administration
of Arg decreases the NTPDase and 5′-nucleotidase activities of rat blood serum, in the present study we investigated the effect
of arginine administration on NTPDase and 5′-nucleotidase activities by synaptosomes from hippocampus of rats. First, sixty-days-old
rats were treated with a single or a triple intraperitoneal injection of arginine (0.8 g/Kg) or an equivalent volume of 0.9%
saline solution (control) and were killed 1 h later. Second, rats received an intracerebroventricular injection of 1.5 mM
arginine solution or saline (5 μL) and were killed 1 h later. We also tested the in vitro effect of arginine (0.1–1.5 mM)
on nucleotide hydrolysis in synaptosomes from rat hippocampus. Results showed that intraperitoneal arginine administration
did not alter nucleotide hydrolysis. On the other hand, arginine administered intracerebroventricularly reduced ATP (32%),
ADP (30%) and AMP (21%) hydrolysis, respectively. In addition, arginine added to the incubation medium, provoked a decrease
on ATP (19%), ADP (17%) and AMP (23%) hydrolysis, respectively. Furthermore, kinetic studies showed that the inhibitory effect
of arginine was uncompetitive in relation to ATP, ADP and AMP. In conclusion, according to our results it seems reasonable
to postulate that arginine alters the cascade involved in the extracellular degradation of ATP to adenosine. 相似文献
2.
Acute Caffeine Treatment Increases Extracellular Nucleotide Hydrolysis from Rat Striatal and Hippocampal Synaptosomes 总被引:5,自引:0,他引:5
da Silva RS Bruno AN Battastini AM Sarkis JJ Lara DR Bonan CD 《Neurochemical research》2003,28(8):1249-1254
The psychostimulant caffeine promotes behavioral effects such as hyperlocomotion, anxiety, and disruption of sleep by blockade of adenosine receptors. The availability of extracellular adenosine depends on its release by transporters or by the extracellular ATP catabolism performed by the ecto-nucleotidase pathway. This study verified the effect of caffeine on NTP-Dase 1 (ATP diphosphohydrolase) and 5-nucleotidase of synaptosomes from hippocampus and striatum of rats. Caffeine and theophylline tested in vitro were unable to modify nucleotide hydrolysis. Caffeine chronically administered in the drinking water at 0.3 g/L or 1 g/L for 14 days failed to affect nucleotide hydrolysis. However, acute administration of caffeine (30 mg/kg, ip) produced an enhancement of ATP (50%) and ADP (32%) hydrolysis in synaptosomes of hippocampus and striatum, respectively. This activation of ATP and ADP hydrolysis after acute treatment suggests a compensatory effect to increase adenosine levels and counteract the antagonist action of caffeine. 相似文献
3.
Bjelobaba I Stojiljkovic M Pekovic S Dacic S Lavrnja I Stojkov D Rakic L Nedeljkovic N 《Cellular and molecular neurobiology》2007,27(6):731-743
Distribution of two enzymes involved in the ectonucleotidase enzyme chain, ecto-nucleoside triphosphate diphosphohydrolase1
(NTPDase1) and ecto-5′-nucleotidase, was assessed by immunohistochemistry in the rat hippocampus. Obtained results have shown
co-expression of the enzymes in the hippocampal region, as well as wide and strikingly similar cellular distribution. Both
enzymes were expressed at the surface of pyramidal neurons in the CA1 and CA2 sections, while cells in the CA3 section were
faintly stained. The granule cell layer of the dentate gyrus was moderately stained for NTPDase1, as well as for ecto-5′-nucleotidase.
Glial association for ecto-5′-nucleotidase was also observed, and fiber tracts were intensively stained for both enzymes.
This is the first comparative study of NTPDase1 and ecto-5′-nucleotidase distribution in the rat hippocampus. Obtained results
suggest that the broad overlapping distribution of these enzymes in neurons and glial cells reflects the functional importance
of ectonucleotidase actions in the nervous system. 相似文献
4.
Patricia C. Marisco Fabiano B. Carvalho Michelle M. Rosa Bruna A. Girardi Jessié M. Gutierres Jeandre A. S. Jaques Ana P. S. Salla Víctor C. Pimentel Maria Rosa C. Schetinger Daniela B. R. Leal Carlos F. Mello Maribel A. Rubin 《Neurochemical research》2013,38(8):1704-1714
Piracetam improves cognitive function in animals and in human beings, but its mechanism of action is still not completely known. In the present study, we investigated whether enzymes involved in extracellular adenine nucleotide metabolism, adenosine triphosphate diphosphohydrolase (NTPDase), 5′-nucleotidase and adenosine deaminase (ADA) are affected by piracetam in the hippocampus and cerebral cortex of animals subjected to scopolamine-induced memory impairment. Piracetam (0.02 μmol/5 μL, intracerebroventricular, 60 min pre-training) prevented memory impairment induced by scopolamine (1 mg/kg, intraperitoneal, immediately post-training) in the inhibitory avoidance learning and in the object recognition task. Scopolamine reduced the activity of NTPDase in hippocampus (53 % for ATP and 53 % for ADP hydrolysis) and cerebral cortex (28 % for ATP hydrolysis). Scopolamine also decreased the activity of 5′-nucleotidase (43 %) and ADA (91 %) in hippocampus. The same effect was observed in the cerebral cortex for 5′-nucleotidase (38 %) and ADA (68 %) activities. Piracetam fully prevented scopolamine-induced memory impairment and decrease of NTPDase, 5′-nucleotidase and adenosine deaminase activities in synaptosomes from cerebral cortex and hippocampus. In vitro experiments show that piracetam and scopolamine did not alter enzymatic activity in cerebral cortex synaptosomes. Moreover, piracetam prevented scopolamine-induced increase of TBARS levels in hippocampus and cerebral cortex. These results suggest that piracetam-induced improvement of memory is associated with protection against oxidative stress and maintenance of NTPDase, 5′-nucleotidase and ADA activities, and suggest the purinergic system as a putative target of piracetam. 相似文献
5.
Mireia Martín-Satué Elise G. Lavoie Michel Fausther Joanna Lecka Elisabet Aliagas Filip Kukulski Jean Sévigny 《Histochemistry and cell biology》2010,133(6):659-668
Extracellular ATP and its hydrolysis product adenosine modulate various reproductive functions such as those requiring contraction,
steroidogenesis, and maintenance of fluid composition. Interestingly, adenosine might act as a key capacitative effector for
mammalian spermatozoa to acquire the capacity for fertilisation. Extracellular nucleotide levels are affected by cell surface
ectonucleotidases, amongst which the ectonucleoside triphosphate diphosphohydrolase (E-NTPDase) family regroups the most abundant
and effective enzymes to hydrolyse ATP and ADP to AMP in physiological conditions. In the male reproductive tract three members
of this family have been indentified: NTPDase1, NTPDase2 and NTPDase3 (Martín-Satué et al. in Histochem Cell Biol 131:615–628,
2009). The purpose of the present study was to characterize in the male reproductive tract the expression profile of the main
enzyme responsible for the generation of adenosine from AMP, namely the ecto-5′-nucleotidase (CD73). The enzyme was identified
by immunological techniques and by in situ enzymatic assays, including inhibition experiments with α,β-methylene-ADP, a specific
CD73 inhibitor. High levels of ecto-5′-nucleotidase were detected in testes in association with both germinal and somatic
cells, in smooth muscle cells throughout the tract, in secretory epithelia from exocrine glands, and remarkably, in principal
cells of epididymis, where co-localization with NTPDase3 was found. The relevance of this co-expression on nucleotide hydrolysis
in these cells directly involved in the control of sperm fluid composition was addressed biochemically. This study suggests
close regulation of extracellular nucleoside and nucleotide levels in the genital tract by ecto-5′-nucleotidase that, in concurrence
with NTPDases, may impact male fertility. 相似文献
6.
Oliveira CB Spanevello R Da Silva AS Souza VC Pimentel VC Thomé GR Schetinger MR Lopes ST Leal DB Monteiro SG 《Experimental parasitology》2011,(3):225-229
This study aimed to evaluate the activities of the ectoenzymes NTPDase and 5′-nucleotidase in synaptosomes from cerebral cortex of rats experimentally infected with Trypanosoma evansi. The animals were divided in four groups (n = 10) according to the time and degree of parasitemia (groups A, B, C and D). The animals from group A were euthanized on day 3 (low parasitemia), group B on day 5 (high parasitemia) and group C on day 15 (low parasitemia). Group D consisted of healthy rats (not-infected, n = 15) and were divided in three periods (n = 5) in order to compare with the infected groups. After euthanasia, cerebral cortex was removed for the preparation of synaptosomes and enzymatic assays. Group A showed no changes in enzymatic activities compared with control. The hydrolysis of ATP, ADP and AMP by the enzymes NTPDase and 5′-nucleotidase were increased (P < 0.05) in group B (38%, 140% and 61%, respectively) when compared with control. In the group C it was observed a decreased (22%) hydrolysis of ATP when compared with control group. The activities of NTPDase and 5′-nucleotidase in synaptosomes alters the acute phase of the disease when the number of circulating parasites is high, thus the change observed is probably due to the parasitemia. 相似文献
7.
Jucimara Baldissarelli Adriana Santi Roberta Schmatz Fátima Husein Abdalla Andréia Machado Cardoso Caroline Curry Martins Glaecir R. Mundstock Dias Nicéia Spanholi Calgaroto Luana Paula Pelinson Karine Paula Reichert Vania Lucia Loro Vera Maria Melchiors Morsch Maria Rosa Chitolina Schetinger 《Cellular and molecular neurobiology》2017,37(1):53-63
Thyroid hormones have an influence on the functioning of the central nervous system. Furthermore, the cholinergic and purinergic systems also are extensively involved in brain function. In this context, quercetin is a polyphenol with antioxidant and neuroprotective properties. This study investigated the effects of (MMI)-induced hypothyroidism on the NTPDase, 5′-nucleotidase, adenosine deaminase (ADA), and acetylcholinesterase (AChE) activities in synaptosomes of rats and whether the quercetin can prevent it. MMI at a concentration of 20 mg/100 mL was administered for 90 days in the drinking water. The animals were divided into six groups: control/water (CT/W), control/quercetin 10 mg/kg, control/quercetin 25 mg/kg, methimazole/water (MMI/W), methimazole/quercetin 10 mg/kg (MMI/Q10), and methimazole/quercetin 25 mg/kg (MMI/Q25). On the 30th day, hormonal dosing was performed to confirm hypothyroidism, and the animals were subsequently treated with 10 or 25 mg/kg quercetin for 60 days. NTPDase activity was not altered in the MMI/W group. However, treatment with quercetin decreased ATP and ADP hydrolysis in the MMI/Q10 and MMI/Q25 groups. 5′-nucleotidase activity increased in the MMI/W group, but treatments with 10 or 25 mg/kg quercetin decreased 5′-nucleotidase activity. ADA activity decreased in the CT/25 and MMI/Q25 groups. Furthermore, AChE activity was reduced in all groups with hypothyroidism. In vitro tests also demonstrated that quercetin per se decreased NTPDase, 5′-nucleotidase, and AChE activities. This study demonstrated changes in the 5′-nucleotidase and AChE activities indicating that purinergic and cholinergic neurotransmission are altered in this condition. In addition, quercetin can alter these parameters and may be a promising natural compound with important neuroprotective actions in hypothyroidism. 相似文献
8.
9.
Members of all four families of ectonucleotidases, namely ectonucleoside triphosphate diphosphohydrolases (NTPDases), ectonucleotide
pyrophosphatase/phosphodiesterases (NPPs), ecto-5′-nucleotidase and alkaline phosphatases, have been identified in the renal
vasculature and/or tubular structures. In rats and mice, NTPDase1, which hydrolyses ATP through to AMP, is prominent throughout
most of the renal vasculature and is also present in the thin ascending limb of Henle and medullary collecting duct. NTPDase2
and NTPDase3, which both prefer ATP over ADP as a substrate, are found in most nephron segments beyond the proximal tubule.
NPPs catalyse not only the hydrolysis of ATP and ADP, but also of diadenosine polyphosphates. NPP1 has been identified in
proximal and distal tubules of the mouse, while NPP3 is expressed in the rat glomerulus and pars recta, but not in more distal
segments. Ecto-5′-nucleotidase, which catalyses the conversion of AMP to adenosine, is found in apical membranes of rat proximal
convoluted tubule and intercalated cells of the distal nephron, as well as in the peritubular space. Finally, an alkaline
phosphatase, which can theoretically catalyse the entire hydrolysis chain from nucleoside triphosphate to nucleoside, has
been identified in apical membranes of rat proximal tubules; however, this enzyme exhibits relatively high K
m values for adenine nucleotides. Although information on renal ectonucleotidases is still incomplete, the enzymes’ varied
distribution in the vasculature and along the nephron suggests that they can profoundly influence purinoceptor activity through
the hydrolysis, and generation, of agonists of the various purinoceptor subtypes. This review provides an update on renal
ectonucleotidases and speculates on the functional significance of these enzymes in terms of glomerular and tubular physiology
and pathophysiology. 相似文献
10.
11.
Matos JA Bruno AN Oses JP Bonan CD Battastini AM Barreto-Chaves ML Sarkis JJ 《Cellular and molecular neurobiology》2002,22(3):345-352
1. Studies have shown that adenosine transport and adenosine A1 receptors in rat brain are subjected to regulation by thyroid hormone levels. Since the ectonucleotidase pathway is an important source of adenosine extracellular, in the present study the in vitro action of T3 and T4 hormones on ectonucleotidase activities in hippocampal synaptosomes was evaluated.2. T3 (Triiodo-l-thyronine) significantly inhibited, in an uncompetitive manner, the ATP and ADP hydrolysis promoted by ATP diphosphohydrolase activity in hippocampal synaptosomes of adult rats.3. In contrast, T4 (Thyroxine) only inhibited ATP hydrolysis in an uncompetitive mechanism, at the concentrations tested (100–500 M), but at the same time did not affect ADP hydrolysis.4. In the present study, we also investigate the in vitro effect of T3 and T4 on 5-nucleotidase activity. However, there are no changes in the activity of this enzyme in the presence of T3 and T4 in the hippocampal synaptosomes of rats.5. These results suggest that thyroid hormones could be involved in the regulation of ectonucleotidase activities, such as ecto-ATP diphosphohydrolase and ecto-ATPase, possibly exerting a modulatory role in extracellular adenosine levels. 相似文献
12.
Spanevello RM de Souza Wyse AT Mazzanti CM Schmatz R Stefanello N Gonçalves JF Bagatini M Battisti V Morsch VM Schetinger MR 《Neurochemical research》2008,33(6):1129-1137
Guanidinoacetate methyltransferase (GAMT) deficiency is a disorder of creatine metabolism characterized by low plasma creatine
concentrations in combination with elevated guanidinoacetate (GAA) concentrations. The aim of this work was to investigate
the in vitro effect of guanidinoacetate in NTPDase, 5′-nucleotidase and acetylcholinesterase activities in the synaptosomes,
platelets and blood of rats. The results showed that in synaptosomes the NTPDase and 5′-nucleotidase activities were inhibited
significantly in the presence of GAA at concentrations of 50, 100, 150 and 200 μM (P < 0.05). However, in platelets GAA at the same concentrations caused a significant increase in the activities of these two
enzymes (P < 0.05). In relation to the acetylcholinesterase activity, GAA caused a significant inhibition in the activity of this enzyme
in blood at concentrations of 150 and 200 μM (P < 0.05), but did not alter the acetylcholinesterase activity in synaptosomes from the cerebral cortex. Our results suggest
that alterations caused by GAA in the activities of these enzymes may contribute to the understanding of the neurological
dysfunction of GAMT-deficient patients. 相似文献
13.
14.
Maria Beatriz Moretto Carine Luísa Lermen Vera Maria Morsch Denise Bohrer Rafael Porto Ineu Adriane Cismoski da Silva Daniela Balz Maria Rosa Chitolina Schetinger 《Journal of trace elements in medicine and biology》2004,17(4):255-260
The aim of the present investigation was to evaluate the effect of a subchronic treatment (30 days/30 doses) with subcutaneous injections (0.1 mg/kg) of HgCl2 on NTPDase (E.C. 3.6.1.5), 5′-nucleotidase (E.C. 3.1.3.5) and acetylcholinesterase (AChE, E.C. 3.1.1.7) activities in brain from adult rats. NTPDase and 5′-nucleotidase were measured in cortical synaptosomal fraction and AChE was measured in the homogenate of cerebral cortex and hippocampus. After the subchronic treatment (30 days), NTPDase activity was enhanced approximately 35% (p < 0.05) with ATP and ADP as substrates and no difference was observed in 5′-nucleotidase activity (AMP hydrolysis). In addition, AChE activity was enhanced in the cerebral cortex (22%, p < 0.05) and hippocampus (26%, p < 0.05) after the subchronic treatment. Mercury deposited in brain was measured by cold vapor (atomic absorption spectrometry) and no difference between the control and the subchronically treated group was observed. Here we showed for the first time that exposure to low levels of Hg2+, which resembles occupational exposure to low levels of mercury, caused a marked increase in NTPDase and AChE activities. The relationship of these alterations with the neurotoxicity of inorganic mercury deserves further studies. 相似文献
15.
Fátima Husein Abdalla Andréia Machado Cardoso Luciane Belmonte Pereira Roberta Schmatz Jamile Fabbrin Gonçalves Naiara Stefanello Amanda Maino Fiorenza Jessié Martins Gutierres Jonas Daci da Silva Serres Daniela Zanini Victor Camera Pimentel Juliano Marchi Vieira Maria Rosa Chitolina Schetinger Vera Maria Morsch Cinthia Melazzo Mazzanti 《Molecular and cellular biochemistry》2013,372(1-2):1-8
This study investigated the effect of quercetin on nucleoside triphosphate diphosphohydrolase (NTPDase), 5′-nucleotidase, adenosine deaminase (ADA), and acetylcholinesterase (AChE) activities in synaptosomes from cerebral cortex of adult rats exposed to cadmium (Cd). Rats were exposed to Cd (2.5 mg/Kg) and quercetin (5, 25 or 50 mg/Kg) by gavage for 45 days. Rats were randomly divided into eight groups (n = 8–10): saline/ethanol, saline/Querc 5 mg/kg, saline/Querc 25 mg/kg, saline/Querc 50 mg/kg, Cd/ethanol, Cd/Querc 5 mg/kg, Cd/Querc 25 mg/kg, and Cd/Querc 50 mg/kg. Results demonstrated that AChE activity increased in the Cd/ethanol group when compared to saline/ethanol group. Treatment with quercetin prevented the increase in AChE activity when compared to Cd/ethanol group. Quercetin treatment prevented the cadmium-induced increase in NTPDase, 5-nucleotidase, and ADA activities in Cd/ethanol group when compared to saline/ethanol group. Our data showed that quercetin have a protector effect against Cd intoxication. This way, is a promising candidate among the flavonoids to be investigated as a therapeutic agent to attenuate neurological disorders associated with Cd intoxication. 相似文献
16.
Bonan Carla Denise Dias Marcelo Medeiros Battastini Ana Maria Oliveira Dias Renato Dutra Sarkis João José Freitas 《Neurochemical research》1998,23(7):977-982
Several lines of evidence indicate that ATP may play an important role in Long-Term Potentiation. In this investigation we evaluated the effect of a memory task (step-down inhibitory avoidance) on the synaptosomal ecto-enzymes (ATP diphosphohydrolase and 5-nucleotidase) involved in the degradation of ATP to adenosine. After the training session, a decrease in the ATPase (40%) and ADPase (29%) activities of ATP diphosphohydrolase as well as was a decrease in 5-nucleotidase activity (31%) was observed in hippocampal synaptosomes of rats trained and killed immediately after training. In synaptosomes of rats killed 30 minutes after training, a decrease in ATPase activity (28%) was observed. In the test session, no significant changes were observed in the enzyme activities studied. These results provide new information about the activity of ecto-enzymes involved in nucleotide degradation and their possible participation in mechanisms of acquisition and modulation of memory processing. 相似文献
17.
18.
Nucleotides and nucleosides play an important role in neurodevelopment acting through specific receptors. Ectonucleotidases
are the major enzymes involved in controlling the availability of purinergic receptors ligands. ATP is co-released with several
neurotransmitters and is the most important source of extracellular adenosine by catabolism exerted by ectonucleotidases.
The main ectonucleotidases are named NTPDases (1–8) and 5′-nucleotidase. Adenosine is a powerful modulator of neurotransmitter
release. Caffeine blocks adenosine receptor activity as well as adenosine-mediated neuromodulation. Considering the susceptibility
of the immature brain to caffeine and the need for correct purinergic signaling during fetal development, we have analyzed
the effects of caffeine exposure during gestational and lactational periods on nucleotide degradation and ectonucleotidase
expression from the hippocampi of 7-, 14- and 21-days-old rats. Nucleotides hydrolysis was assessed by colorimetric determination
of inorganic phosphate released. Ectonucleotidases expression was performed by RT-PCR. ATP and ADP hydrolysis displayed parallel
age-dependent decreases in both control and caffeine-treated groups. AMP hydrolysis increased with caffeine treatment in 7-days-old
rats (75%); although there was no significant difference in AMP hydrolysis between control (non caffeine-treated) rats and
14- or 21-days caffeine-treated rats. ADP hydrolysis was not affected by caffeine treatment. Caffeine treatment in 7- and
14-days-old rats decreased ATP hydrolysis when compared to the control group (19% and 60% decrease, respectively), but 21-days-treated
rats showed an increase in ATP hydrolysis (39%). Expression levels of NTPDase 1 and 5 decreased in hippocampi of caffeine-treated
rats. The expression of 5′-nucleotidase was not affected after caffeine exposure. The changes observed in nucleotide hydrolysis
and ectonucleotidases expression could promote subtle effects on normal neural development considering the neuromodulatory
role of adenosine. 相似文献
19.
Fátima Husein Abdalla Andréia Machado Cardoso Roberta Schmatz Jamile Fabbrin Gonçalves Jucimara Baldissarelli Caroline Curry Martins Daniela Zanini Lizielle Souza de Oliveira Pauline da Costa Victor Camera Pimentel Luciane Belmonte Pereira Cibele Lima Lhamas Maria Rosa Chitolina Schetinger Vera Maria Morsch Cinthia Melazzo Andrade Mazzanti 《Molecular and cellular biochemistry》2014,396(1-2):201-211
The ex vivo and in vitro effects of quercetin on NTPDase, adenosine deaminase (ADA), and acetycholinesterase (AChE) activities in lymphocytes, as well as the effects of quercetin on butyrylcholinesterase (BChE) activity in serum and myeloperoxidase (MPO) activity in plasma were determined in rats. For the ex vivo experiment, animals were orally exposed to Cadmium (Cd) for 45 days. Animals were divided into eight groups: saline/ethanol, saline/Querc 5 mg/kg, saline/Querc 25 mg/kg, saline/Querc 50 mg/kg, Cd/ethanol, Cd/Querc 5 mg/kg, Cd/Querc 25 mg/kg, and Cd/Querc 50 mg/kg. The ex vivo data showed an increase in the ATP and ADP hydrolysis and ADA activity in Cd-exposed rats when compared to the control group. The treatment with quercetin 25 and 50 mg/kg prevented this increase in the ATP and ADP hydrolysis, while the treatment with quercetin 5, 25, and 50 mg/kg prevented the increase in the ADA activity. AChE, BChE, and MPO activities ex vivo presented an increase in the Cd-exposed group when compared to the control group, and the treatment with quercetin 5, 25, and 50 mg/kg prevented this increase caused by Cd exposure. The in vitro experiment showed that quercetin 5, 10, 25, or 50 µM decreased the ADA activity proportionally to the increase of the concentrations of quercetin when compared to the control group. Thus, we can suggest that the quercetin is able to modulate NTPDase, ADA, AChE, and MPO activities and contribute to maintain the levels of ATP, adenosine, and acetylcholine normal, respectively, exhibiting potent pro-inflammatory and anti-inflammatory actions. 相似文献
20.
Ecto-nucleotidases play a pivotal role in terminating the signalling via ATP and in producing adenosine, a neuromodulator in the nervous system. We have now investigated the pattern of adenosine formation with different concentrations of extracellular ATP in rat hippocampal nerve terminals. It was found that adenosine formation is delayed with increasing concentrations of ATP. Also, the rate of adenosine formation increased sharply when the extracellular concentrations of ATP + ADP decrease below 5 M, indicating that ATP/ADP feed-forwardly inhibit ecto-5-nucleotidase allowing a burst-like formation of adenosine possibly designed to activate facilitatory A2A receptors. Initial rate measurements of ecto-5-nucleotidase in hippocampal nerve terminals, using IMP as substrate, showed that ATP and ADP are competitive inhibitors (apparent Ki of 14 and 4 M). In contrast, in hippocampal immunopurified cholinergic nerve terminals, a burst-like formation of adenosine is not apparent, suggesting that channelling processes may overcome the feed-forward inhibition of ecto-5-nucleotidase, thus favouring A1 receptor activation. 相似文献