Background
CGS 21680 is a selective agonists of A2 adenosine receptor with IC50 value of 22nM [1].
CGS 21680 is found to be potent and selective adenosine A2 receptor agonists. In a radioligand binding in vitro assay, CGS 21680 binds A2 receptor with IC50 value of 22nM and the A1/A2 ratio is 141, In the perfused rat heart model, CGS 21680 can increase coronary flow with greater EC25 value than 1000nM. It shows a good separation between its ability to induce vasorelaxation and bradycardia. CGS 21680 also has potent effect on blood pressure in vivo with EC25 value of 9μg/kg and it can induce an increase in heart rate [1].
It is reported that CGS 21680 also has the potency of anti-inflammatory. It can reduce the development of acute lung inflammation in a mouse model of carrageenan-induced pleurisy. In both prior and post-treatment, CGS 21680 can reduce the number of inflammatory cells and the degree of lung injury [2].
参考文献:
[1] Alan J. Hutchison, Randy L. Webb, Howard H. Oei, Geetha R. Ghai, Mark B. Zimmerman and Michael Williams. CGS 21680C, an A2 Selective Adenosine Receptor Agonist with Preferential Hypotensive Activity. The Journal of Pharmacology and Experimental Therapeutics. 1989, 25 (1): 47-55.
[2] Daniela Impellizzeri, Rosanna Di Paola, Emanuela Esposito, Emanuela Mazzon, Irene Paterniti, Alessia Melani, Placido Bramanti, Felicita Pedata, Salvatore Cuzzocrea. CGS 21680, an agonist of the adenosine (A2A) receptor, decreases acute lung inflammation. European Journal of Pharmacology. 2011, 68: 305-316.
Protocol
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Vitro experiment [1,2]:
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Samples
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Hippocampal and striatal slices
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Preparation method
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The solubility of this compound in DMSO is > 19.3 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.
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Reacting condition
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EC50: 110 nM
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Applications
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In hippocampal slices, CGS 21680 appeared to be a weak agonist on pre- and postsynaptic measures of electrophysiological activity (putative A1 receptor mediated events) and was ineffective at stimulating the formation of cAMP (a putative A2b mediated response). In striatal slices, CGS 21680 potently stimulated the formation of cAMP with an EC50 of 110 nM but was ineffective at inhibiting electrically stimulated dopamine release. CGS21680 (10 nM) showed only small survival activity, but the activity was significantly enhanced by the addition of a phosphodiesterase inhibitor, IBMX. The survival activity of CGS21680 on cultured motoneurons was exerted by mixed effects of the adenylate cyclase-cAMP-PKA pathway and the transactivation of neurotrophin receptors.
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Animal experiment [3,4]:
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Animal models
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Female Lewis rats
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Dosage form
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Intraperitoneal injection, 1 mg/kg, every two days
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Application
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In female Lewis rats, CGS21680 (1 mg/kg/i.p.) intervention promoted the development of EAN. CGS21680 intervention promoted inflammatory cell infiltration and demyelination of sciatic nerves. CGS21680 intervention elevated the levels of P0 peptide-specific antibodies in serum. CGS21680 intervention suppressed Th1 and Th17 cytokines, and powerfully inhibited lymphocyte proliferation and IL-2 secretion. CGS21680 intervention reduced the proportions CD4+Foxp3+ Treg cells while increased CD4+CXCR5+ Tfh cells, B cells and dendritic cells in draining lymph nodes. CGS21680 intervention increased the expressions of MHC class II and CD86. CGS21680 (0.1 mg/kg, i.p.) transiently increased heart frequency. Following transient MCAo, CGS21680 at both doses protected from neurological deficit from the first day up to 7 days thereafter. CGS21680 reduced microgliosis, astrogliosis and improved myelin organization in the striatum and cytoarchitecture of the ischemic cortex and striatum. Two days after transient MCAo, CGS21680 reduced the number of infiltrated granulocytes into the ischemic tissue.
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Other notes
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Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
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参考文献:
[1]. Lupica C R, Cass W A, Zahniser N R, et al. Effects of the selective adenosine A2 receptor agonist CGS 21680 on in vitro electrophysiology, cAMP formation and dopamine release in rat hippocampus and striatum[J]. Journal of Pharmacology and Experimental Therapeutics, 1990, 252(3): 1134-1141.
[2]. Komaki S, Ishikawa K, Arakawa Y. Trk and cAMP-dependent survival activity of adenosine A 2A agonist CGS21680 on rat motoneurons in culture[J]. Neuroscience letters, 2012, 522(1): 21-24.
[3]. Zhang M, Li X L, Li H, et al. Activation of the adenosine A 2A receptor exacerbates experimental autoimmune neuritis in Lewis rats in association with enhanced humoral immunity[J]. Journal of neuroimmunology, 2016, 293: 129-136.
[4]. Melani A, Corti F, Cellai L, et al. Low doses of the selective adenosine A 2A receptor agonist CGS21680 are protective in a rat model of transient cerebral ischemia[J]. Brain research, 2014, 1551: 59-72.
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