The most widely recognized effects of adenosine

The most widely recognized effects of adenosine are operated through inhibiting A1R, one of the most abundant G protein-coupled receptors in sigma receptor tissue [53]. A1R are located presynaptically, postsynaptically and nonsynaptically [54]. Effect of adenosine in neuronal circuits of adult mammals is to selectively depress excitatory transmission by acting presynaptic A1R [55]. Postsynaptic A1R density can influence the responsiveness to excitatory stimuli by a simultaneous control of N-type calcium channels and NMDA receptors. Selective A1R agonists or antagonists have been reported to impair or facilitate learning and memory, respectively [56], [57]. However, our results showed that cordycepin reduced the density of A1R in the hippocampal DG area of mice only at dose of 10mg/kg rather than 5mg/kg, suggesting that the improvement of cordycepin on short-term spatial memory may play a very small part in reducing A1R density in the hippocampus.
Conclusion
Conflict of interest
Acknowledgements Funding for this research was provided by the Science and Technology Foundation of Guangzhou (201510010171) and China Education Ministry for Scholarship Foundation (20131205).
Introduction Adenosine is produced during conditions of metabolic stress and high cellular activity to increase oxygen supply and decrease oxygen consumption. Adenosine is mainly generated by the 5′-nucleotidases, which catalyze the dephosphorylation of adenosine monophosphate (AMP) into adenosine. Intracellular adenosine levels are mainly regulated by adenosine kinase, which converts adenosine into AMP, while extracellular adenosine levels are regulated by adenosine deaminase, which degrades adenosine to inosine (Blackburn, 2003, Ham and Evans, 2012, Wen and Xia, 2012). Adenosine binds to a family of four P1 G-protein coupled receptors; namely A1, A2A, A2B, and A3 adenosine receptor. Their activation is implicated in the modulation of renal and cardiovascular function as well as erectile function (Headrick et al., 2013, Labazi et al., 2016b, Layland et al., 2014, Phatarpekar et al., 2010, Vallon and Osswald, 2009, Wen and Xia, 2012). Recently, adenosine was described as an endothelium-derived hyperpolarizing factor due to its ability to relax and hyperpolarize vascular smooth muscle cells (Ohta et al., 2013). Vascular studies from our laboratory and others have demonstrated that, while A1 and A3 adenosine receptor activation results in vasoconstriction, A2Aand A2B adenosine receptor activation results in vasodilation (Ansari et al., 2007, El-Awady et al., 2011, El-Gowelli et al., 2013, Hein et al., 2013, Kunduri et al., 2013b, Labazi et al., 2016a, Labazi et al., 2016b, Nayeem et al., 2008, Sanjani et al., 2011, Tawfik et al., 2005, Teng et al., 2013). However, the contribution of each receptor to overall vascular tone regulation can be animal- or tissue-specific. For instance, our laboratory and others demonstrated that adenosine-mediated vasorelaxation in murine mesenteric arteries is A2B adenosine receptor-dependent (Teng et al., 2013, Wang et al., 2010), while others showed that adenosine-mediated vasorelaxation in rat and rabbit mesenteric arteries is mainly dependent upon the A2A adenosine receptor (de Brito et al., 2002, Hiley et al., 1995). Type I diabetes (T1D) is a metabolic disease characterized by a deficit in insulin secretion resulting in increased blood glucose levels. In the U.S., a recently published study showed that the prevalence of T1D in youth has increased by 21.1% (Hamman et al., 2014). Additionally, chronic diabetes causes damage to several organ systems. In the vasculature, the effect of diabetes can be divided into microvascular (retinopathy, nephropathy, and cardiomyopathy) and macrovascular (cardiovascular diseases and erectile dysfunction) complications, with cardiovascular disease being the leading cause of morbidity and mortality in diabetic patients (Shi and Vanhoutte, 2009). Few studies have reported that cell- and tissue-specific changes in adenosine receptor expression can be altered in disease states such as diabetes (Bender et al., 2009, Duarte et al., 2006, Grden et al., 2005, Grden et al., 2007, Labazi et al., 2016a, Pawelczyk et al., 2005). However, not much is known about the changes in adenosine receptor expression and/or signaling in the vasculature. In the present study, we sought to investigate the effect of T1D on adenosine receptor–mediated regulation of vascular tone in the aorta and mesenteric arteries.