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1.
Chinese Journal of Lung Cancer ; (12): 460-467, 2022.
Artigo em Chinês | WPRIM | ID: wpr-939732

RESUMO

Adenosine is a metabolite produced abundantly in the tumor microenvironment, dampening immune response in inflamed tissues via adenosine A2A receptor (A2AR) which is widely expressed on immune cells, inhibiting anti-tumor immune response accordingly. Therefore, blocking adenosine signaling pathway is of potential to promote anti-tumor immunity. This review briefly introduces adenosine signaling pathway, describes its role in regulating tumor immunity and highlights A2AR blockade in cancer therapy. Prospective anti-tumor activity of adenosine/A2AR inhibition has been revealed by preclinical data, and a number of clinical trials of A2AR antagonists are under way. Primary results from clinical trials suggest that A2AR antagonists are well tolerated in cancer patients and are effective both as monotherapy and in combination with other therapies. In the future, finding predictive biomarkers are critical to identify patients most likely to benefit from adenosine pathway blockade, and further researches are needed to rationally combine A2AR antagonists with other anti-tumor therapies.
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Assuntos
Humanos , Adenosina/uso terapêutico , Antagonistas do Receptor A2 de Adenosina/uso terapêutico , Neoplasias Pulmonares , Receptor A2A de Adenosina/metabolismo , Microambiente Tumoral
2.
Acta cir. bras ; 31(2): 133-137, Feb. 2016. graf
Artigo em Inglês | LILACS | ID: lil-775559

RESUMO

PURPOSE: To investigate the role of adenosine A2A receptors on 6-OHDA-induced motor disorder in rat. METHODS: In order to induce experimental model of Parkinson's disease, 6-hydoxydopamine (8 μg/rat) was injected unilaterally into the SNc. After three weeks as a recovery period, 6-OHDA-induced bradykinesia and balance disturbances were assessed by using beam traversal test 10, 30 and 60 minutes after intraperitoneal injections of the drugs (caffeine, SCH58261). RESULTS: The results showed that 6-OHDA (8 μg/rat, Intra-SNc) induced motor disorders of Parkinson's disease and increased elapsed time in the beam test (p<0.001). Injection of caffeine (30 mg/kg, i.p.) and SCH58261 (2 mg/kg, i.p.) attenuated elapsed time on beam (p<0.01 and p<0.001). We showed that acute administration of caffeine and SCH 58261 can improve the 6-OHDA-induced bradykinesia and motor disturbance. CONCLUSION: Adenosine A2AR antagonists improve 6-OHDA-motor deficit and this effect seems to be mediated by the inhibition of A2A presynaptic receptors in substantia nigra pars compacta.


Assuntos
Animais , Masculino , Doença de Parkinson Secundária/induzido quimicamente , Cafeína/farmacologia , Oxidopamina/efeitos adversos , Antagonistas de Receptores Purinérgicos P1/farmacologia , Antagonistas do Receptor A2 de Adenosina/farmacologia , Estudos de Tempo e Movimento , Ratos Wistar , Hipocinesia/induzido quimicamente , Modelos Animais de Doenças , Transtornos Motores/induzido quimicamente , Atividade Motora/efeitos dos fármacos
3.
Cell Journal [Yakhteh]. 2012; 14 (3): 231-236
em Inglês | IMEMR | ID: emr-153862

RESUMO

Ecstasy, also known as 3, 4-methylenedioxymethamphetamine [MDMA], is a psychoactive recreational hallucinogenic substance and a major worldwide recreational drug. There are neurotoxic effects observed in laboratory animals and humans following MDMA use. MDMA causes apoptosis in neurons of the central nervous system [CNS]. Withdrawal signs are attenuated by treatment with the adenosine receptor [A2A receptor]. This study reports the effects of glutamyl cysteine synthetase [GCS], as an A2A receptor agonist, and succinylcholine [SCH], as an A2A receptor antagonist, on Sprague Dawley rats, both in the presence and absence of MDMA. In this experimental study, we used seven groups of Sprague Dawley rats [200-250 g each]. Each group was treated with daily intraperitoneal [IP] injections for a period of one week, as follows: i. MDMA [10 mg/kg]; ii. GCS [0.3 mg/kg]; iii. SCH [0.3 mg/kg]; iv. GCS + SCH [0.3 mg/kg each]; v. MDMA [10 mg/kg] + GCS [0.3 mg/kg]; vi. MDMA [10 mg/kg] + SCH [0.3 mg/kg]; and vi. normal saline [1 cc/kg] as the sham group. Bax [apoptotic protein] and Bcl-2 [anti-apoptotic protein] expressions were evaluated by striatum using RT-PCR and Western blot analysis. There was a significant increase in Bax protein expression in the MDMA+SCH group and a significant decrease in Bcl-2 protein expression in the MDMA+SCH group [p<0.05]. A2A receptors have a role in the apoptotic effects of MDMA via the Bax and Bcl-2 pathways. An agonist of this receptor [GCS] decreases the cytotoxcity of MDMA, while the antagonist of this receptor [SCH] increases its cytotoxcity


Assuntos
Animais de Laboratório , N-Metil-3,4-Metilenodioxianfetamina/efeitos adversos , Receptores Purinérgicos P1 , Agonistas do Receptor A2 de Adenosina , Antagonistas do Receptor A2 de Adenosina , Proteína de Suscetibilidade a Apoptose Celular , Receptores A2 de Adenosina
4.
Acta Pharmaceutica Sinica ; (12): 742-746, 2011.
Artigo em Chinês | WPRIM | ID: wpr-348890

RESUMO

This study is to examine the sedative, hypnotic and anticonvulsive effects of an adenosine analogue, WS090501. The spontaneous locomotor activity was recorded by open field equipment, and the EEG of rats was recorded by polyphysiograph. Pentylenetetrazol (PTZ)-induced seizure model was used. The spontaneous locomotor activity was decreased by WS090501 at various doses (0.06, 0.13, and 0.25 mg x kg(-1)), and the decreasing rate was 28.4%, 47.1% and 61.2% respectively. Furthermore, the effect of WS090501 on spontaneous locomotor activity of mice can be antagonized by DPCPX, a selective adenosine A1R antagonist, but cannot be antagonized by SCH58261, a selective adenosine A2AR antagonist. The NREM sleep was significantly increased by WS090501 (0.05 and 0.2 mg x kg(-1)), and the increasing rate was 27.6% and 102.8%, respectively, at 6th hour after administration. The REM sleep decreased significantly at the higher dose. PTZ induced serious convulsion in mice. The latency of convulsion was prolonged, and the number of seizure and mortality decreased after administration of WS090501. These results show that WS090501 has potent sedative, hypnotic and anticonvulsive effects, which may be mediated through adenosine A1R.


Assuntos
Animais , Masculino , Camundongos , Ratos , Adenosina , Farmacologia , Antagonistas do Receptor A1 de Adenosina , Farmacologia , Antagonistas do Receptor A2 de Adenosina , Farmacologia , Anticonvulsivantes , Farmacologia , Convulsivantes , Eletroencefalografia , Hipnóticos e Sedativos , Farmacologia , Camundongos Endogâmicos ICR , Atividade Motora , Pentilenotetrazol , Pirimidinas , Farmacologia , Ratos Wistar , Convulsões , Sono , Triazóis , Farmacologia , Xantinas , Farmacologia
5.
Acta Pharmaceutica Sinica ; (12): 1199-1203, 2011.
Artigo em Chinês | WPRIM | ID: wpr-233012

RESUMO

This study is to investigate the effect of compound B2 on the damage of PC12 cells induced by serum deprivation and to explore its related mechanisms. The binding characteristics of B2 to rat striatum adenosine A2A receptor was studied by radioligand 3H-MSX-2 binding assay. Cell viability was detected by MTT assay. ROS formation was measured after DCFDA fluorescent staining. B2 has affinity to rat adenosine A2A receptor (K1 = 0.37 micromol x L(-1)). B2 remarkably increased PC12 cell survival rate in serum deprivation-induced PC12 cells. The percentage of serum deprivation-induced death of PC12 was 49.6%, and the treatment of B2 (0.1-100 micromol x L(-1)) increased the cell viability to 63.3%, 74.9%, 86.3% and 88.1%, respectively. Adenosine A2A receptor antagonist SCH 58261 could significantly block the protective effect of B2. The cell viability with 0.1 micromol x L(-1) SCH 58261 decreased by 16.1%, 24.0% and 19.8%, in the presence of B2 (0.1-10 micromol x L(-1)). Serum deprivation-induced ROS formation was 3.5 times more than that of control group, and treatment with B2 significantly and dose-dependently inhibited ROS over-formation. The protective effect of B2 may be related with adenosine A2A receptor. Decrease of serum-deprivation induced ROS formation may also be one of the mechanisms.


Assuntos
Animais , Feminino , Masculino , Ratos , Adenosina , Metabolismo , Farmacologia , Antagonistas do Receptor A2 de Adenosina , Farmacologia , Sobrevivência Celular , Corpo Estriado , Metabolismo , Meios de Cultura Livres de Soro , Células PC12 , Pirimidinas , Farmacologia , Ratos Wistar , Espécies Reativas de Oxigênio , Metabolismo , Receptor A2A de Adenosina , Metabolismo , Triazóis , Farmacologia
6.
Acta Pharmaceutica Sinica ; (12): 241-246, 2008.
Artigo em Chinês | WPRIM | ID: wpr-268138

RESUMO

A2B adenosine receptor is involved in the control of mast cell degranulation, interleukin-8 synthesis and cell growth. A2B adenosine receptor antagonists may serve as novel drugs for asthma, Alzheimer' s disease, cystic fibrosis and type-II diabetes. Therefore, seeking for the highly selective A2B adenosine receptor antagonists has been one of great interest. The molecular basis, structure-activity relationship of selective A2B adenosine receptor antagonists and their interactions with A2B adenosine receptor were reviewed.


Assuntos
Animais , Humanos , Adenosina , Farmacologia , Antagonistas do Receptor A2 de Adenosina , Antagonistas do Receptor A3 de Adenosina , Adenosina-5'-(N-etilcarboxamida) , Farmacologia , Usos Terapêuticos , Antiasmáticos , Usos Terapêuticos , Asma , Tratamento Farmacológico , Artéria Pulmonar , Relação Estrutura-Atividade , Xantinas , Farmacologia
7.
Acta Pharmaceutica Sinica ; (12): 716-720, 2006.
Artigo em Chinês | WPRIM | ID: wpr-294952

RESUMO

<p><b>AIM</b>To study the effect of AMP579 and adenosine on potassium ionic (K+) or sodium ionic (Na+) channels and to elucidate ionic mechanisms underlying negative inotropic and antiarrhythmic effects of AMP579 and adenosine.</p><p><b>METHODS</b>Ionic channel currents of rat and guinea pig ventricular myocytes were recorded by patch clamp technique in whole-cell configuration.</p><p><b>RESULTS</b>Adenosine showed a stronger activating effect on transient outward K+ current (I(to)) than AMP579, EC50 of adenosine and AMP579 were 2.33 and 8. 32 micromol x L(-1), respectively (P < 0.05). An adenosine A1 receptor blocker, 1,3-dipropyl-8-cyclopentylxanthine (PD116948), can abolish the effects of AMP579 and adenosine on I(to), demonstrating that the effect is mediated by adenosine A1 receptor. Adenosine exerted a more obvious inhibitory effect on delayed rectifier K+ current (IK) than AMP579. IC50 of adenosine and AMP579 were 1.21 and 2.31 micromol x L(-1), respectively (P < 0.05). AMP579 had a more powerful inhibitory effect on inward rectifier K+ current (IK1) than adenosine. IC50 of AMP579 and adenosine were 4.15 and 20.7 micromol x L(-1), repectively (P < 0.01). AMP579 and adenosine exerted a similar inhibitory effect on fast inward Na+ current (INA), IC50 of AMP579 and adenosine were 9.46 and 6.23 micromol x L(-1), respectively (P > 0.05).</p><p><b>CONCLUSION</b>Adenosine showed a stronger activating effect on I(to) than AMP579, however, the mechanism of AMP579 and adenosine activating I(to) was mediated by adenosine A1 receptor. AMP579 has a more powerful inhibitory effect on IK1, and less inhibitory effect on IK than adenosine. Both drugs have a similar inhibitory effect on INa. The negative inotropic and antiarrhythmic effects are related to these ionic mechanisms.</p>


Assuntos
Animais , Masculino , Ratos , Adenosina , Química , Farmacologia , Antagonistas do Receptor A1 de Adenosina , Antagonistas do Receptor A2 de Adenosina , Relação Dose-Resposta a Droga , Estimulação Elétrica , Cobaias , Ventrículos do Coração , Biologia Celular , Imidazóis , Química , Farmacologia , Potenciais da Membrana , Estrutura Molecular , Miócitos Cardíacos , Biologia Celular , Fisiologia , Canais de Potássio , Fisiologia , Canais de Potássio Corretores do Fluxo de Internalização , Fisiologia , Piridinas , Química , Farmacologia , Ratos Wistar , Canais de Sódio , Fisiologia , Teobromina , Farmacologia , Xantinas , Farmacologia
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