Navegando por Palavras-chave "Adenosine"
Agora exibindo 1 - 10 de 10
Resultados por página
Opções de Ordenação
- ItemAcesso aberto (Open Access)Adenosine A(2A) receptor agonist (CGS-21680) prevents endotoxin-induced effects on nucleotidase activities in mouse lymphocytes(Elsevier B.V., 2011-01-25) Vuaden, Fernanda Cenci; Savio, Luiz Eduardo Baggio; Bastos, Carolina Maria Alves [UNIFESP]; Bogo, Mauricio Reis; Bonan, Carla Denise; Pontificia Univ Catolica Rio Grande do Sul; Univ Fed Rio Grande do Sul; Universidade Federal de São Paulo (UNIFESP)Adenosine 5'-triphosphate (ATP) released during inflammation presents proinflammatory properties. Adenosine, produced by catabolism of ATP, is an anti-inflammatory compound. Considering the role of ATP and adenosine in inflammation and the importance of ectonucleotidases in the maintenance of their extracellular levels, we investigated the effect of a selective agonist of the adenosine A(2A) receptor (CGS-21680) on ectonucleotidase activities and gene expression patterns in lymphocytes from mice submitted to an endotoxemia model. Animals were injected intraperitoneally with 12 mg/kg Lipopolyssacharide (LPS) and/or 0.5 mg/kg CGS-21680 or saline. Nucleotidase activities were determined in lymphocytes from mesenteric lymph nodes and analysis of ectonucleotidase expression was carried out by a semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Exposure to endotoxemia promoted an increase in nucleotide hydrolysis. When CGS-21680 was administered concomitantly with LPS, this increase was prevented for ATP, adenosine 5'-monophosphate (AMP), and p-Nitrophenyl thymidine 5'-monophosphate (p-Nph-5'-TMP) hydrolysis. However, when CGS-21680 was administered 24 h after LPS injection, the increase was not reversed. the expression pattern of ectonucleotidases was not altered between LPS and LPS plus CGS-21680 groups, indicating that the transcriptional control was not involved on the effect exerted for CGS-21680. These results showed an enhancement of extracellular nucleotide catabolism in lymphocytes after induction of endotoxemia, which was prevented, but not reversed by CGS-21680 administration. These findings suggest that the control of nucleotide and nucleoside levels exerted by CGS-21680 could contribute to the modulation of the inflammatory process promoted by adenosine A(2A) agonists. (C) 2010 Elsevier B.V. All rights reserved.
- ItemSomente MetadadadosAvaliação dos efeitos da hipóxia neonatal no desenvolvimento da esquizofrenia: papel do sistema adenosinérgico(Universidade Federal de São Paulo (UNIFESP), 2020-08-14) Ramos, Aline Camargo [UNIFESP]; Calzavara, Mariana Bendlin [UNIFESP]; Universidade Federal de São PauloRecently, efforts have been made in understanding the role of neurodevelopment in schizophrenia. It is believed that the manifestation of schizophrenia, reflecting the striatal hyperdopaminergic state, is the result of changes that emerge from the interaction between genetic, environmental and neurodevelopment-related factors throughout life. The pharmacotherapy of schizophrenia based on the dopaminergic hypothesis remains unsatisfactory for the treatment of negative symptoms and cognitive deficits related to this disease. Adenosine is a homeostatic modulator capable of affecting different complex networks such as neurotransmitter-dependent pathways, bioenergetics and epigenetics. In this sense, adenosine appears to be a promising candidate in correcting the functional imbalance found in schizophrenia, and may influence the dopaminergic and glutamatergic systems. Evidence points out to an important participation of adenosine in neural development and indicates a potential involvement of this substance in the etiology of schizophrenia. Perinatal hypoxia is one of the most well-established risk factors for the development of schizophrenia. However, there are few studies adressing the mechanisms related to the role of hypoxia in the pathophysiology of schizophrenia. Systems subjected to hypoxia have reported increased adenosine levels as one of the adaptive responses. Many of these effects evolve to permanent changes that are still not well understood, which may have an important role in the pathophysiology of numerous diseases, including schizophrenia. Animal and cellular models can be interesting tools for the study of interventions such as perinatal hypoxia and its repercussions on brain and behavioral function that mimic the changes observed in schizophrenia. Hence, the objective of this work was to study the effects of neonatal chemical hypoxia on the development of schizophrenia, evaluating the role of the adenosinergic system in the modulation of the dopaminergic system as a participant factor in the pathophysiology of schizophrenia. Therefore, Wistar rats were treated with cobalt chloride, a chemical hypoxiainducing compound, in the neonatal period (7 days of age). These animals were subjected to behavioral tests at young age (50 days) to assess whether they had xx behavioral changes related to the first psychotic episode. In adulthood (90 days),animals were tested in paradigms that analyze behavioral changes related to schizophrenia, such as locomotion, social interaction and context-based fear. Molecular tests were performed in samples from the brain of these animals in order to check the expression of genes related to hypoxia and also neuronal patterns. Our results showed that rats treated with cobalt chloride in the neonatal period showed behavioral changes related to schizophrenia at young and adult age compared to animals that received saline solution. These animals had increased expression of HIF-1α and VEGF and reduced immunoreactivity of parvalbuminpositive interneurons in the prefrontal cortex as adults compared to animals from the control group. We observed that the behavioral changes were reversed by the acute use of haloperidol antipsychotic and that the use of caffeine, but not selective adenosinergic antagonists, previously the administration of cobalt chloride was able to prevent the changes firstly observed. Finally, we note that the changes observed in animals that received cobalt chloride were similar to those observed in animals from the SHR strain, which is used as an animal model for the study of schizophrenia. Thus, we can suggest that chemical hypoxia in the neonatal period causes behavioral and neuronal changes related to schizophrenia in rats, reinforcing that neonatal hypoxia is a risk factor for the later development of schizophrenia. The participation of the adenosinergic system in the pathophysiology of schizophrenia is supported by the results obtained in this work, since the use of caffeine as a pretreatment was able to prevent the behavioral changes caused by chemical hypoxia. Caffeine, by antagonizing adenosine receptors, normalizes the transmission that has been altered by chemical hypoxia, indicating the importance of adequate levels of adenosine for normal neurodevelopment. Situations that alter this transmission, such as hypoxia, impair brain development and increase the risk of psychiatric disorders, such as schizophrenia.
- ItemAcesso aberto (Open Access)Differential neuroprotection by A(1) receptor activation and A(2A) receptor inhibition following pilocarpine-induced status epilepticus(Elsevier B.V., 2011-10-01) Rosim, Fernanda Elisa [UNIFESP]; Persike, Daniele Suzete [UNIFESP]; Nehlig, Astrid; Amorim, Rebeca Padrão [UNIFESP]; Oliveira, Daniela Mara de; Fernandes, Maria Jose da Silva [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); INSERM; Universidade de Brasília (UnB)Aiming at a better understanding of the role of A(2A) in temporal lobe epilepsy (TLE), we characterized the effects of the A(2A) antagonist SCH58261 (7-(2-phenylethyl)-5-amino-2(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c] pyrimidine) on seizures and neuroprotection in the pilocarpine model. the effects of SCH58261 were further analyzed in combination with the A(1) agonist R-Pia (R(-)-N-6-(2)-phenylisopropyl adenosine). Eight groups were studied: pilocarpine (Pilo), SCH + Pilo, R-Pia + Pilo, R-Pia + SCH + Pilo, Saline, SCH + Saline, R-Pia + Saline, and R-Pia + SCH + Saline. the administration of SCH58261, R-Pia, and R-Pia + SCH58261 prior to pilocarpine increased the latency to SE, and decreased either the incidence of or rate of mortality from SE compared with controls. Administration of R-Pia and R-Pia + SCH58261 prior to pilocarpine reduced the number of Fluoro-Jade B-stained cells in the hippocampus and piriform cortex when compared with control. This study showed that pretreatment with R-Pia and SCH58261 reduces seizure occurrence, although only R-Pia has neuroprotective properties. Further studies are needed to clarify the neuroprotective role of A(2A) in TLE. (C) 2011 Elsevier Inc. All rights reserved.
- ItemSomente MetadadadosEffects of A1 receptor agonist/antagonist on spontaneous seizures in pilocarpine-induced epileptic rats(Academic Press Inc Elsevier Science, 2016) Amorim, Beatriz Oliveira; Hamani, Clement; Ferreira, Elenn; Miranda, Maisa Ferreira; Fernandes, Maria Jose S.; Rodrigues, Antonio M.; de Almeida, Antonio-Carlos G.; Covolan, LucieneAdenosine is an endogenous anticonvulsant that activates pre- and postsynaptic adenosine A(1) receptors. A(1) receptor agonists increase the latency for the development of seizures and status epilepticus following pilocarpine administration. Although hippocampal adenosine is increased in the chronic phase of the pilocarpine model, it is not known whether the modulation of A(1) receptors may influence the frequency of spontaneous recurrent seizures (SRS). Here, we tested the hypothesis that the A(1) receptor agonist RPia ([R]-N-phenylisopropyladenosine) and the A(1) antagonist DPCPX (8-Cyclopentyl-1,3-dipropylxanthine) administered to chronic pilocarpine epileptic rats would respectively decrease and increase the frequency of SRS and hippocampal excitability. Four months after Pilo-induced SE, chronic epileptic rats were video-monitored for the recording of SRS before (basal) and after a 2-week treatment with RPia (25 mu g/kg) or DPCPX (50 mu g/kg). Following sacrifice, brain slices were studied with electrophysiology. We found that rats given RPia had a 93% nonsignificant reduction in the frequency of seizures compared with their own pretreatment baseline. In contrast, the administration of DPCPX resulted in an 87% significant increase in seizure rate. Nontreated epileptic rats had a similar frequency of seizures along the study. Corroborating our behavioral data, in vitro recordings showed that slices from animals previously given DPCPX had a shorter latency to develop epileptiform activity, longer and higher DC shifts, and higher spike amplitude compared with slices from nontreated Pilo controls. In contrast, smaller spike amplitude was recorded in slices from animals given RPia. In summary, the administration of A(1) agonists reduced hippocampal excitability but not the frequency of spontaneous recurrent seizures in chronic epileptic rats, whereas A(1) receptor antagonists increased both. (C) 2016 Elsevier Inc. All rights reserved.
- ItemAcesso aberto (Open Access)Estudo do bloqueio do receptor adenosinérgico A2A no modelo experimental de epilepsia induzida por pilocarpina(Universidade Federal de São Paulo (UNIFESP), 2009-05-27) Rosim, Fernanda Elisa [UNIFESP]; Fernandes, Maria Jose da Silva [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Adenosine is an important endogenous neuromodulator with anticonvulsant and neuroprotective properties. The present work studied the effect of blocking the adenosinergic A2A receptor by selective antagonist SCH58261, associated or not, the activation of A1 receptor by agonist R-Pia in the seizures modulation and neuroprotection of the brain areas vulnerable to injury in the pilocarpine model. Eight groups were studied: Pilo, SCH+Pilo, RPia+ Pilo, R-Pia+SCH+Pilo, Saline, SCH+Saline, R-Pia+Saline, RPia+ SCH+Saline. The behavioral parameters: number of animals that developed status epilepticus, latency to the beginning of SE and mortality rate after the insult were evaluated. Through the technique of FJ-B, evaluated the neurodegeneration and through the technique of immunohistochemistry, the caspase -1 expression in brain regions, 24 hours and 7 days after SE. The results showed that pre-treatment with SCH58261, R-Pia and the combination of both reduced the number of animals in SE, increased the threshold for the establishment of the SE and decreased the mortality rate after the insult, compared to pilocarpine treatment. The pre-treatment with R-Pia e R-Pia + SCH58261 reduces the intensity of marking by FJ-B in CA3, hilus of dentate gyrus and piriform cortex after 24 hours and 7 days of the SE, compared to pilocarpine treatment. The caspase -1 expression, 24 hours after the SE, was intense in the amygdala, and moderate in the piriform and entohrinal cortex and absent in the hippocampus, whereas, 7 days after SE, the expression was intense in the hippocampus and amygdala, discreet in the cortex entohrinal and moderate in the piriform cortex in all groups, except in the controls. We conclude that the A2A antagonist have potent anticonvulsant effect, but does not promote neuroprotection in brain areas vulnerable to injury, while the A1 agonist, has a crucial role in the modulation of seizures and promotes significant neuroprotection in the pilocarpine model.
- ItemAcesso aberto (Open Access)Heart injury following intestinal ischemia reperfusion in rats is attenuated by association of ischemic preconditioning and adenosine(Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia, 2014-01-01) Montero, Micaela Frasson; Saurim, Rafael; Bonservizi, Wesley Guedes Sava; Koike, Marcia Kiyomi; Taha, Murched Omar [UNIFESP]; ABC Medical School; Universidade Federal de São Paulo (UNIFESP); São Paulo University Faculty of MedicinePURPOSE: To investigate the effect of ischemic preconditioning (IPC) and adenosine as strategies to protect cardiac injury caused by intestinal IR in rats, based on increasing in adenosine bioavailability and improvement of cell energy state by IPC.METHODS:Male Wistar rats were submitted to 60 minutes of intestinal ischemia and 120 minutes of reperfusion. Intravenous injections of saline or Adenosine (AD) was administered five minutes before ischemia, five minutes before reperfusion and after 55 minutes reperfusion. Cardiac samples were obtained, fixed in formalin solution, embedded in paraffin, and sections of 5 μm were stained by hematoxylin-eosin. Histological analysis of myocardium was performed according occurrence of necrosis signs: piknosis, band contraction, eosinophilic cytoplasm, karyorrhexis and vacuolization (score - zero to 5).RESULTS:The groups submitted to ischemia alone (I=4.0), and reperfusion (IR=4.5) showed highest level of lesion compared to the others (I+IPC=3.3, IR+IPC=3.6, I+AD=3.0, IR+AD=3.8). The most interesting result was association of IPC and AD in IR model (IR+IPC+AD=1.2, p=0.002), showing preservation of the heart tissue, with fibers showing typical cross-striations and nuclei characteristics. Rare and small areas of tissue necrosis was observed and suggestion of capillaries congestion.CONCLUSION: Intestinal ischemia reperfusion promotes cardiac tissue injury. Ischemic preconditioning in association with adenosine is an efficient strategy to protect the heart against ischemia and reperfusion injury.
- ItemAcesso aberto (Open Access)Interaction between saliva's adenosine and tick parasitism: effects on feeding and reproduction(Biomed Central Ltd, 2017) Anatriello, Elen [UNIFESP]; Freire Oliveira, Carlo Jose; Oliveira, Nathalia Baptista; Fisch, Andressa; Milanezi, Cristiane Maria; da Silva, Joao Santana; Ferreira de Miranda-Santos, Isabel Kinney; Ferreira, Beatriz RossettiBackground: It has recently been demonstrated that saliva from Rhipicephalus sanguineus ticks contains adenosine (ADO) and prostaglandin E2 (PGE2), two non-protein molecules that have significant immunomodulatory properties. These molecules can inhibit cytokine production by dendritic cells (DCs), while also reducing the expression of CD40 in these cells. However, more studies are needed for a better understanding of their participation in the feeding of ticks in vivo. This work, therefore, evaluated the importance of ADO during tick infestations. Mice were infested with adult ticks (3 couples/mouse), and their skin was collected at the tick-infested site (3rd and 7th day), and mRNA for receptors of ADO was quantified by real-time PCR. Results: Tick infestation increased by four and two times the expression of the A2b and A3v1 receptors on day 3, respectively, while expression of other ADO receptors was unaltered. In addition, we treated mice (n = 10/group) daily with 8-(p-Sulfophenyl) theophylline, 8-pSPT, 20 mg/kg, i.p.), a non-selective antagonist of ADO receptors, and evaluated the performance of ticks during infestations. Female ticks fed on 8-pSPT-treated mice presented a reduction in their engorgement, weight and hatching rates of egg masses, and survival times of larvae compared to the same parameters presented by ticks in the control group. To investigate if these 8-pSPT-treated mice presented altered immune responses, we performed three tick infestations and collected their lymph node cells to determine the percentages and activation state of DCs and cytokine production by lymphocytes by flow cytometry (Cytometric Bead Array technique, CBA). Our data showed that 8-pSPT-treated mice presented an increase in the percentage of DCs as well as of their stimulatory and co-stimulatory molecules (CD40, CD80 and MHCII). Regarding production of T cell cytokines, we observed a significant increase in the levels of IL-2 and a significant decrease in IL-10, IL-17, TNF-alpha and IFN-gamma cytokines. Conclusions: These results suggest that ADO produced by ticks helps them feed and reproduce and that this effect may be due to modulation of host DCs and T cells.
- ItemSomente MetadadadosIs adenosine associated with sudden death in schizophrenia? A new framework linking the adenosine pathway to risk of sudden death(Pergamon-Elsevier Science Ltd, 2018) Gadelha, Ary [UNIFESP]; Zugman, Andre [UNIFESP]; Calzavara, Mariana Bendlin [UNIFESP]; de Mendonca Furtado, Remo Holanda; Scorza, Fulvio Alexandre [UNIFESP]; Bressan, Rodrigo Afonsecca [UNIFESP]Schizophrenia is associated with an increased mortality from cardiovascular disease. Relatively few studies have assessed the putative association of schizophrenia pathophysiology with sudden death. Low adenosine levels have been associated with schizophrenia. In cardiology, increased mortality among patients with congestive heart failure has been associated with genetic polymorphisms that potentially lead to lower adenosine levels. Thus, we hypothesize that adenosine could link schizophrenia and cardiovascular mortality, with decreased adenosine levels leading to increased vulnerability to hyperexcitability following hypoxic insults, increasing the odds of fatal arrhythmias. Low adenosine levels might also lead to a small increase in overall mortality rates and a major increase in the sudden death rate. This hypothesis paves the way for further investigation of the increased cardiac mortality associated with schizophrenia. Potentially, a better characterization of adenosine related mechanisms of sudden death in schizophrenia could lead to new evidence of factors leading to sudden death in the general population.
- ItemAcesso aberto (Open Access)Papel dos receptores de adenosina e da PKA no prejuízo de memória causado pela privação de sono(Universidade Federal de São Paulo (UNIFESP), 2017-12-20) Oliveira, Sophia La Banca de [UNIFESP]; Hipólide, Débora Cristina [UNIFESP]; http://lattes.cnpq.br/6303382961871353; http://lattes.cnpq.br/7411925710894750; Universidade Federal de São Paulo (UNIFESP)Sleep deprivation (SD) impairs various cognitive functions, including different types of memory. Various neurotransmitters and neuromodulators signaling pathways are altered by SD, including adenosine signaling. Adenosine is a neuromodulator which acts as the main homeostatic regulator of sleep, its extracellular concentrations raise in various regions of the brain during SD. The behavioral effects of adenosine are dependent mainly on its actions on two receptors, the A1, a Gi protein coupled receptor, and A2A, a Gs protein coupled receptor. A1 receptor activation impairs memory formation, while the role of A2A receptor on memory formation is not well understood yet. Among the main intracellular signaling pathways modulated by adenosine are the protein kinase A (PKA) pathway and the exchange protein activated by cAMP (EPAC) pathway. Both enzimes are involved on the induction of long term potentiation (LTP), a cellular correlate of memory. Considering this background we suggest that adenosine has an important role in the memory impairment caused by SD through the activation of the adenosine receptors on the brain regions recruited during memory formation, such as the hippocampus and the striatum, and by consequent modulation of the PKA and EPAC pathways. To test this hypothesis we first evaluated the effect of 96 hours of SD through the multiple platform modified method on the levels of the A1 and A2A receptors on the hippocampus. We also used the phosphorylation of PKA to infer its activity. We observed that sleep deprivation decreased the levels of A2A receptor and phosphorylation of PKA, but had no effect on the A1 receptor levels. Then we tested the effect of DPCPX, an antagonist of the A1 receptor, on the performance of sleep deprived animals on two memory tasks, the multiple trial inhibitory avoidance (MTIA) and the contextual fear conditioning (CFC), and the effect of an A2A agonist, CGS 21680, and an A2A antagonist, ZM 241385, on the MTIA. The results showed that DPCPX prevented the impairment on the performance on the MTIA, but not on the CFC. While CGS 21680 had no effect on the performance on the MTIA, ZM 241385 impaired the xix performance of the control animals and increased the performance of the sleep deprived animals. We also tested the effect of SD and DPCPX on the levels of the A1 receptors in the phosphorylation of PKA and activation of EPAC in the striatum and hippocampus after the training session of the MTIA. SD increased the levels of A1 receptor on the striatum, but not in the hippocampus, DPCPX had no effect on neither structures. SD decreased PKA phosphorylation on both structures, DPCPX prevented this effect on the striatum, but not on the hippocampus. SD had no effect on the activity of EPAC. Finally, we tested the effect of drugs which act on other neurotransmitter systems on the phosphorylation of PKA on the hippocampus of animals subjected to the training session of the MTIA. We replicated the result that indicated a decrease on PKA phosphorylation and reverted it with the administration of d-ciclosserin, a NMDA coagonist. The alteration on the level of A2A receptors on the hippocampus and A1 receptors in the striatum indicates that SD has an impact on adenosine signaling on both structures. The activation of PKA on the hippocampus in the time interval between 30 minutes and 6 hours after the MTIA training session is necessary for memory consolidation. Its activation is also necessary for the LTP formation in the striatum. Thus, the decrease of the phosphorylation on these structures caused by SD after the MTIA training may be related to the effects of SD on memory. MTIA task has an instrumental component on which structures of the striatum are involved, this does not happen on the CFC, thus the effect of DPCPX on the MTIA, but not on the CFC may be related to the A1 receptors on the striatum, but not on the hippocampus. This result, as well as the increase on the levels of A1 receptors and the reversion of the decrease of PKA phosphorylation on the striatum indicate that the A1 receptors on the striatum have an important role on the performance impairment on MTIA caused by SD. On the other hand, DPCPX did not prevent the impairment on the CFC nor the decrease of the phosphorylation of PKA on the hippocampus, indicating that another neurotransmitter system would be involved on the impairment on this task. The reversion of the decrease of phosphorylation caused by the dciclosserin suggests an involviment of the NMDA receptors.
- ItemSomente MetadadadosParticipação Do Ampc Extracelular Na Regulação Da Transmissão Neuromuscular Esquelética(Universidade Federal de São Paulo (UNIFESP), 2017-09-28) Duarte, Thiago [UNIFESP]; Godinho, Rosely Oliveira [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Introduction: In skeletal muscle, the intracellular cyclic AMP regulates processes that include the contraction, metabolism, and expression of synaptic proteins (Duarte et al., 2001; Bergantin et al. 2011). Studies of our group have shown that after the activation of GsPCR or adenylyl cyclase, part of the newly formed intracellular cAMP is transported to the cellular interstitium (Godinho and Costa-Jr 2003; Chiavegatti et al., 2008). The cAMP is able to act as an extracellular signaling molecule through its metabolite adenosine, formed by the sequential action of ecto-phosphodiesterases and ecto-5'-nucleotidases (Chiavegatti et al., 2008). More recently, we have demonstrated that β2 adrenoceptor activation has a biphasic action characterized by the initial potentiation of muscle contraction resulting from the increase of intracellular cAMP, followed by a negative inotropic effect, related to cAMP efflux and activation of A1 receptors by the adenosine metabolite (Duarte et al, 2012). It is known that adenosine formed from ATP released by the motor neuron is able to modulate neuromuscular transmission through its adenosine metabolite and activation of neuronal adenosine receptors (Ribeiro J.A, et al., 1996), but in skeletal muscle, It was not identified whether the efflux and metabolism of cAMP, regulates the neuromuscular transmission Objective: Evaluate the participation of extracellular cAMP and its metabolite adenosine in neuromuscular transmission. Methods: Male diaphragm muscles were used for 3 to 4 months, and muscle contraction was induced by electrical stimulation of the phrenic nerve (n = 3-4). The train-of-four TOF electrical stimulation protocol (2 Hz, 2 ms duration) was used and the ratio between the contraction amplitude of the fourth (T4) and the first stimulus (T1) was determined to evaluate the effect of the neuromuscular blockers d-tubocurarine and hexamethonium in the presence or absence of cAMP, clenbuterol and / or formoterol, with or without preincubation of adenosine receptor antagonists (CGS15943 and ZM241385) or inhibitors of organic anion (probenecid) ecto-5'-nucleotidase (AMPCP). The effect of formoterol on intra- and extracellular cAMP was quantified by time resolving-FRET assay.Results: 300 nM d-tubocurarine and 1.5 mM hexamethonium caused 25% neuromuscular block, this effect was inhibited by the 30 min preincubation with 100 μM cAMP and by the agonists of β2adenoceptors 100 nM clenbuterol and 100 nM formoterol which also promoted a 15% increase in contraction force, these effects were associated with increased of intracellular and extracellular cAMP levels. The adenosine receptor antagonists 100 nM CGS15943 (non-selective) and 100 nM ZM241385 (A2A selective) and the inhibitors of organic anion (300 μM probenecid) and ecto-5'-nucleotidase (100 μM AMPCP) inhibited the effect cAMP and clenbuterol on d-tubocurarine and hexamethonium-induced tetanic fade. Conclusions: The results presented in this work show that the extracellular cAMP adenosine pathway initiated by activation of post-synaptic β2 adrenoceptors modulates the contraction of skeletal muscle induced by phrenic nerve stimulation. These modulations depend on efflux of cAMP and activation of presynaptic adenosine receptors and probably involve increment in ACh release. However, this pathway can act as a paracrine signaling that creates feedback loop and regulation between muscle fibers and motor neurons.