AR-R 17779 hydrochloride 是一种有效的、选择性的 nAChR 完全激动剂，对 α7 和 α4β2 亚型的 Kis 分别为 92 和 16000 nM。
AR-R 17779 is a selective agonist of α7 nicotinic acetylcholine receptor (α7-nAChR) [1] with an EC50 of 21 μM to rat α7-nAChRs expressed in Xenopus oocytes [2].
Nicotine enhances cognitive functions, e.g. learning, attention, retention and memory in both humans and animals, via activation of brain nicotinic acetylcholine receptors (nAChRs). These receptors are homo- or heteropentameric ligand-gated ion channels. The most common nicotinic receptors found in the brain are the α4β2-nAChR and the α7-nAChR [3].
The expression of CD38, CD138, and Bcl-6, was sensitive to regulation via nAChRs. Daudi cells exposed to AR-R 17779 ± methyllycaconitine (MLA) resulted in only moderate changes in the gene expression of CD38, CD138 and Bcl-6, but AR-R 17779 alone significantly (P< 0.05) increased protein levels of CD38 and CD138. That means the effect of AR-R 17779 was abolished by MLA [4].
Cholesterol is necessary for the homeostasis of acetylcholine receptor (AChR) levels for ion translocation and at the plasmalemma [5]. In ApoE-deficient mice, AR-R 17779 significantly reduced atherosclerotic plaque area in the thoracic aorta, and lowered heart rate, blood pressure, serum triglyceride level and serum total cholesterol level compared with which in Ang II + HFD mice. Treatment with AR-R 17779 in mice did not result in any sickness behavior or apparent abnormalities. At the end of the experiment, the serum concentration of AR-R 17779 was 1.18 ± 0.17 μM. In ApoE-deficient mice, treatment with AR-R 17779 resulted in significantly reduced aortic diameter comparable to control mice (0.81 ± 0.11 mm, p< 0.0001 vs. Ang II + HFD) [1].
参考文献:
[1].? Toru Hashimoto, Toshihiro Ichiki, AyaWatanabe, et al. Stimulation of α7 nicotinic acetylcholine receptor by AR-R17779 suppresses atherosclerosis and aortic aneurysm formation in apolipoprotein E-deficient mice. Vascular Pharmacology, 2014, 61:49-55.
[2].? Rudy Schreiber, Marion Dalmus and Jean De Vry. Effects of α4/β2- and α7-nicotine acetylcholine receptor agonists on prepulse inhibition of the acoustic startle response in rats and mice. Psychopharmacology, 2002, 159:248-257.
[3].? Marja van Kampen, Karin Selbach, Renate Schneider, et al. AR-R 17779 improves social recognition in rats by activation of nicotinic α7 receptors. Psychopharmacology, 2004, 172:375-383.
[4].? Juan Arredondo, Denys Omelchenko, Alexander I Chernyavsky, et al. Functional role of the nicotinic arm of the acetylcholine regulatory axis in human B-cell lines. Journal of Experimental Pharmacology, 2009, 1:1-7.
[5].? Virginia Borroni and Francisco J. Barrantes. Cholesterol Modulates the Rate and Mechanism of Acetylcholine Receptor Internalization. J. Biol. Chem., 2011, 286(19):17122-32.
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