Adenosine receptor subtype-selective antagonists in inflammation and hyperalgesia
Adenosine receptor subtype-selective antagonists in inflammation and hyperalgesia
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DOI：
10.1007/s00210-007-0252-9
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发表时间：
2008-03-01
影响因子：
3.6
通讯作者：
Zimmer, Andreas
中科院分区：
文献类型：
--
作者：
Bilkei-Gorzo, Andras;Abo-Salem, Osama M.;Zimmer, Andreas
在这项研究中，我们检测了全身和局部给药亚型选择性腺苷受体拮抗剂PSB-36、PSB-1115、MSX-3和PSB-10对炎症和炎症性痛觉过敏的影响。全身应用拮抗剂后，腺苷受体亚型的药物阻断通常导致福尔马林注射后水肿形成减少，除了a(3)受体拮抗剂外，卡拉胶注射后也是如此。选择性A（2B）受体拮抗剂PSB-1115在卡拉胶试验中表现出双相、剂量依赖效应，低剂量时增加水肿形成，高剂量时减少水肿形成。A(1)和A（2B）拮抗剂在福尔马林试验的第一阶段减轻了疼痛相关行为，而A（2B）和A(3)拮抗剂在第二阶段炎症期减轻。A（2B）拮抗剂在减轻炎症性疼痛方面具有剂量依赖性，在低剂量为3mg /kg时达到最大效果。10mg /kg剂量的A（2A）拮抗剂MSX-3完全消除炎症性痛觉过敏。与A(1)拮抗剂不同，A（2A）、A（2B）和A(3)受体的选择性拮抗剂在局部给药时也具有活性。我们的研究结果表明，腺苷受体亚型的阻断可以降低炎症反应的程度。选择性A（2A）拮抗剂可用于治疗炎症性痛觉过敏，而A（2B）拮抗剂有可能作为治疗炎症性疼痛的镇痛药物。
In this study, we examined the effects of systemic and local administration of the subtype-selective adenosine receptor antagonists PSB-36, PSB-1115, MSX-3, and PSB-10 on inflammation and inflammatory hyperalgesia. Pharmacological blockade of adenosine receptor subtypes after systemic application of antagonists generally led to a decreased edema formation after formalin injection and, with the exception of A(3) receptor antagonism, also after the carrageenan injection. The selective A(2B) receptor antagonist PSB-1115 showed a biphasic, dose-dependent effect in the carrageenan test, increasing edema formation at lower doses and reducing it at a high dose. A(1) and A(2B) antagonists diminished pain-related behaviors in the first phase of the formalin test, while the second, inflammatory phase was attenuated by A(2B) and A(3) antagonists. The A(2B) antagonist was particularly potent in reducing inflammatory pain dose-dependently reaching the maximum effect at a low dose of 3 mg/kg. Inflammatory hyperalgesia was totally eliminated by the A(2A) antagonist MSX-3 at a dose of 10 mg/kg. In contrast to the A(1) antagonist, the selective antagonists of A(2A), A(2B), and A(3) receptors were also active upon local administration. Our results demonstrate that the blockade of adenosine receptor subtypes can decrease the magnitude of inflammatory responses. Selective A(2A) antagonists may be useful for the treatment of inflammatory hyperalgesia, while A(2B) antagonists have potential as analgesic drugs for the treatment of inflammatory pain.