NECA is a non-selective agonist of adenosine receptors [1]. NECA regulates intracellular cAMP levels by activating adenosine receptors, thereby affecting many cellular physiological processes, such as anti-inflammation, vasodilation, inhibition of neuronal activity, cardioprotection, and immune regulation [2-3].
In H9c2 cells, NECA (0.1–10μM; 20min) blocked H2O2-induced GSK-3β phosphorylation and GRP94 expression [4]. In skeletal muscle cells, NECA (100nM, 10μM; 19h) modulates CPT1B, stimulates LCAD, inhibits ACCβ mRNA gene expression [5]. In HREC cells, NECA (10μM; 24-72h) induced a time-dependent increase in cell proliferation [6].
In ex-hypoxic polycythemic mice model, NECA (0.05, 0.1µmol/kg; iv; single injection) significantly increased serum erythropoietin levels in mice with hypoxic erythrocytosis [7]. In mice that were only immunized, intranasal NECA (50μL; 1mM; intranasal administration; single administration) administration caused a significant increase in bronchoalveolar lavage total cell count (TCC), neutrophils and eosinophils [8].
References:
[1]. Knapp C M, Foye M M, Cottam N, et al. Adenosine agonists CGS 21680 and NECA inhibit the initiation of cocaine self-administration[J]. Pharmacology Biochemistry and Behavior, 2001, 68(4): 797-803.
[2]. Elsherbiny N M, Abd El Galil K H, Gabr M M, et al. Reno-protective effect of NECA in diabetic nephropathy: implication of IL-18 and ICAM-1[J]. European Cytokine Network, 2012, 23(3): 78-86.
[3]. Li L, Chen J, Wang Z, et al. NECA alleviates inflammatory responses in diabetic retinopathy through dendritic cell toll-like receptor signaling pathway[J]. Frontiers in Immunology, 2024, 15: 1415004.
[4]. Xing F, Han H, He Y, et al. Roles of endoplasmic reticulum stress in NECA‐induced cardioprotection against ischemia/reperfusion injury[J]. Oxidative Medicine and Cellular Longevity, 2017, 2017(1): 2490501.
[5]. Haddad M. The effect of NECA, CGS 21680, PSB 603 on fatty acid transport and oxidation in skeletal muscle cells[J]. International Journal of Pharmaceutical Sciences and Research, 2016, 7(12): 4827.
[6]. Grant M B, Davis M I, Caballero S, et al. Proliferation, migration, and ERK activation in human retinal endothelial cells through A2B adenosine receptor stimulation[J]. Investigative ophthalmology & visual science, 2001, 42(9): 2068-2073.
[7]. Nakashima J, Ohigashi T, Brookins J W, et al. Effects of 5′-N-ethylcarboxamideadenosine (NECA) on erythropoietin production[J]. Kidney international, 1993, 44(4): 734-740.
[8]. El-Hashim A Z, Abduo H T, Rachid O M, et al. Intranasal administration of NECA can induce both anti-inflammatory and pro-inflammatory effects in BALB/c mice: Evidence for A2A receptor sub-type mediation of NECA-induced anti-inflammatory effects[J]. Pulmonary Pharmacology & Therapeutics, 2009, 22(3): 243-252.
NECA是一种非选择性腺苷受体激动剂 [1]。NECA通过激活腺苷受体调节细胞内cAMP水平，从而影响多种细胞生理过程，例如抗炎、血管舒张、抑制神经元活动、心脏保护和免疫调节 [2-3]。
在H9c2细胞中，NECA（0.1-10μM；20分钟）可阻断H2O2诱导的GSK-3β磷酸化和GRP94表达 [4]。在骨骼肌细胞中，NECA（100nM，10μM；19h）可调节CPT1B，刺激LCAD，并抑制ACCβ mRNA基因表达 [5]。在HREC细胞中，NECA（10μM；24-72h）可诱导细胞增殖，且呈时间依赖性增加 [6]。
在缺氧性红细胞增多症小鼠模型中，NECA（0.05，0.1µmol/kg；iv；单次注射）显著提高缺氧性红细胞增多症小鼠血清促红细胞生成素水平 [7]。在仅免疫的小鼠中，经鼻给予NECA（50μL；1mM；经鼻给药；单次给药）可显著增加支气管肺泡灌洗液总细胞计数（TCC）、中性粒细胞和嗜酸性粒细胞 [8]。