Background
NECA is a non-selective agnonist of adenosine receptor with the concentration of 10 μM [1].
Adenosine is an important endogenous signaling molecule and plays a pivotal role in regulating a wide range of physiological functions, such as immune system response and inflammation, via cooperated with its receptor. It has been shown that adenosine receptor agonists can be either anti-inflammatory or proinflammatory, and the dual role of the adenosine receptor agonists causing these opposing effects should provide a better guide for therapeutic intervention used for different diseases in clinic [2].
When tested with primary murine microglia cells, NECA treatment significantly inhibited the productions of CXCL10 and TNF-αinduced by LPS [1, 3].
In CD73(-/-) mice model infected with T. gondii cysts, administration of NECA protected CD73(-/-) mice against T. gondii-induced immunopathology via agonist adenosine receptor, which suggested that CD73-generated adenosine was critical for immune regulation during T.gondii infection [1]. In a mouse model with human uveitis, injection of NECA at an early stage after immunization with peptides 1-20 inhibited effect on both Th1 and Th17 responses [1, 4]. When tested with adult male Wistar rats of amygdala-kindled seizures, intravenous infusion of NECA after administration of PHT increased the PHT level in brain compared with control group by antognisting adenosine receptor thus strengthened the anticonvulsant properties of PHT against amygdala kindled seizures [5].
NECA是腺苷受体的非选择性激动剂，浓度为10 μM [1]。
腺苷是一种重要的内源性信号分子，通过与其受体协同作用，发挥调节多种生理功能的关键作用，如免疫系统反应和炎症等。已经证明，腺苷受体激动剂既可以是抗炎性的，也可以是促炎性的，腺苷受体激动剂引起这些相反效应的双重作用应该为临床上不同疾病的治疗干预提供更好的指导 [2]。
在小鼠原代小胶质细胞中进行实验，NECA处理显著抑制了LPS诱导的CXCL10和TNF-α产生[1，3]。在感染T. gondii囊泡的CD73（-/-）小鼠模型中，NECA的给药通过激动腺苷受体保护CD73（-/-）小鼠免受T. gondii诱导的免疫病理损伤，这表明CD73产生的腺苷在T.gondii感染期间的免疫调节中至关重要 [1]。在一个人类葡萄膜炎小鼠模型中，NECA注射可以在免疫肽1-20免疫后的早期阶段抑制Th1和Th17反应的作用[1，4]。在Wistar大鼠的杏仁核痉挛模型中，PHT给药后静脉注射NECA可以通过拮抗腺苷受体增强PHT的抗癫痫性质，从而增加脑内PHT水平[5]。
参考文献:
[1].?? ?Mahamed, D.A., L.E. Toussaint, and M.S. Bynoe, CD73-Generated Adenosine Is Critical for Immune Regulation during Toxoplasma gondii Infection. Infect Immun, 2015. 83(2): p. 721-9.
[2].?? ?Solomou, S. and M. Korbonits, The role of ghrelin in weight-regulation disorders: Implications in clinical practice. Hormones (Athens), 2014. 13(4): p. 458-475.
[3].?? ?Newell, E.A., et al., 2',3'-cAMP, 3'-AMP, 2'-AMP and adenosine inhibit TNF-alpha and CXCL10 production from activated primary murine microglia via A2A receptors. Brain Res, 2015. 1594: p. 27-35.
[4].?? ?Liang, D., et al., Anti-inflammatory or proinflammatory effect of an adenosine receptor agonist on the Th17 autoimmune response is inflammatory environment-dependent. J Immunol, 2014. 193(11): p. 5498-505.
[5].?? ?Sun, Z., et al., Activation of Adenosine Receptor Potentiates the Anticonvulsant Effect of Phenytoin Against Amygdala Kindled Seizures. CNS Neurol Disord Drug Targets, 2014.
Protocol
Animal experiment: | Male Wistar rats are used in this experiment. These animals range in weight between 350 and 425 g. They are housed individually in hanging wire cages under a 12-h light/dark cycle. The effects of 5'-N-Ethylcarboxamidoadenosine (NECA) are tested in four rats. In the experiment, either 5'-N-Ethylcarboxamidoadenosine (NECA) (5, 7.5, 10, 20 μg/kg) or vehicle (saline) is administered intraperitoneally 15 min prior to the start of test sessions. 5'-N-Ethylcarboxamidoadenosine (NECA) is administered following a random order crossover design. In most cases, animals are tested twice with the same dose[1]. |
参考文献: [1]. Knapp CM, et al. Adenosine agonists CGS 21680 and NECA inhibit the initiation of cocaine self-administration. Pharmacol Biochem Behav. 2001 Apr;68(4):797-803.
[2]. Elsherbiny NM, et al. Reno-protective effect of NECA in diabetic nephropathy: implication of IL-18 and ICAM-1. Eur Cytokine Netw. 2012 Jul-Sep;23(3):78-86. |
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