Abrogation of adenosine A1 receptor signalling improves metabolic regulation in mice by modulating oxidative stress and inflammatory responses

Abstract

Aims/hypothesis Adenosine is an important regulator of metabolism; however, the role of the A 1 receptor during ageing and obesity is unclear. The aim of this study was to investigate the effects of A 1 signalling in modulating metabolic function during ageing. Methods Age-matched young and aged A 1 (also known as Adora1)-knockout (A 1 −/−) and wild-type (A 1 +/+ ) mice were used. Metabolic regulation was evaluated by body composition, and glucose and insulin tolerance tests. Isolated islets and islet arterioles were used to detect islet endocrine and vascular function. Oxidative stress and inflammation status were measured in metabolic organs and systemically. Results Advanced age was associated with both reduced glucose clearance and insulin sensitivity, as well as increased visceral adipose tissue (VAT)

Genetic Abrogation of Adenosine A 3 Receptor Prevents Uninephrectomy and High Salt–Induced Hypertension

“…Because mRNA expression of all 3 Ang II receptors (AT 1A , AT 1B and AT 2 ) was similar between groups in our study (Figure S3), it seems unlikely that differential AT receptor activation between the genotypes plays a key role in disease development in this model. Moreover, interaction between Ang II and adenosine A 1 or A 2 receptor signaling on the renal arterioles modulates nitric oxide and bioavailability, which has been reported to influence renal hemodynamics during health and in the progression of renal, cardiovascular, and metabolic disorders . Less is known about the A 3 receptor, although a recent study suggested a modulatory role in renal microcirculation.…”

“…Mice were anesthetized with isoflurane, and fat and lean body masses were measured using dual‐emission x‐ray absorptiometry (GE Medical‐Lunar), as described previously …”

Behavioral changes induced through adenosine A2A receptor ligands in a rat depression model induced by olfactory bulbectomy

“…The bars represent the means ± SD (n = 10 −2 ), Two-way ANOVA was used to evaluate differences between groups (*p < .05, **p < .01, ***p < .001 indicate significant differences compared to the sham group). The different letters (a and b) represent significant differences adenosine and ZM treatment on BW changes could be associated to A1 receptors instead of A2AR as suggest Yang et al (2015) (Yang et al, 2015). Our results indicated that only chronic administration of the A2AR antagonist ZM reduced the time rats spent motionless and increased struggling behavior.…”

“…In contrast, adenosine treatment achieves weight recovery of OBX rats; thus, the different results between adenosine and ZM treatment on BW changes could be associated to A1 receptors instead of A2AR as suggest Yang et al. () (Yang et al., ). Our results indicated that only chronic administration of the A2AR antagonist ZM reduced the time rats spent motionless and increased struggling behavior.…”

Pharmacological targeting of adenosine receptor signaling

“…This has already been reported in relation to the role of A 1 AR or A 2A AR in brain injury (Aden et al, 2003;Chen et al, 1999;Cunha, 2005;Turner et al, 2003) and in relation to metabolic abnormalities, contradictory findings related to the A 1 and A 2B receptors could be attributed to the different developmental stages (Csoka et al, 2014;Figler et al, 2011;Johansson et al, 2007;Yang et al, 2015). Moreover, in various disease models both protective and detrimental effects of adenosine receptor activation have been observed depending on the stage of the disorder confirming the high complexity of the adenosine receptor-mediated M A N U S C R I P T…”