Animal models for the study of adenosine receptor function

Abstract

Adenosine receptors represent a family of G-protein coupled receptors that are ubiquitously expressed in a wide variety of tissues. This family contains four receptor subtypes: A1 and A3, which mediate inhibition of adenylyl cyclase; and A2a and A2b, which mediate stimulation of this enzyme. Currently, all receptor subtypes have been genetically deleted in mouse models except for the A2b adenosine receptor, and some have been overexpressed in selective tissues of transgenic mice. Studies involving these transgenic mice indicated that receptor levels are rate limiting, as effects were amplified upon increases in receptor level. The knockout models pointed to clusters of activities related to the physiologies of the cardiovascular and the nervous systems, which are either reduced or enhanced upon specific receptor deletion. Interestingly, the trend of effects on these systems is similar in the A1 and A3 adenosine receptor knockout mice and opposite to the effects observed in the A2a adenosine receptor knockout model. This review summarizes in vitro studies on pathways affected by each adenosine receptor, and primarily focuses on the above in vivo models generated to investigate the physiologic role of adenosine receptors. Furthermore, it illustrates the need for multiple adenosine receptor subtype deficiency studies in mice and the deletion of the A2b subtype.

Adenosine: An immune modulator of inflammatory bowel diseases

“…A2bR is the only receptor expressed in epithelial cells of cecum and colon. A3R can be detected in jejunum and proximal colon [45,46] . Adenosine receptors are members of the G protein-coupled family of receptors [47] .…”

Modulation of murine dendritic cell function by adenine nucleotides and adenosine: Involvement of the A2B receptor

“…As reported by Yaar et al [29], the A 2B adenosine receptor is coupled to G s and/or G q protein and mediates its effect by activating adenylyl cyclase and/or phospholipase C. In order to study phospholipase C activation, we have measured intracellular calcium accumulation by flow cytometry. As shown in Fig.…”

Detection of inflamed atherosclerotic lesions with diadenosine-5′,5‴- P 1 , P 4 -tetraphosphate (Ap 4 A) and positron-emission tomography

“…Extracellular adenosine nucleotides are released from a variety of cells and regulate many physiologic activities by interaction with P2 receptors or adenosine nucleotide receptors (9)(10)(11)(12). The development of atherosclerosis is closely associated with upregulation of the extracellular purinergic receptor P2Y 2 R, whose activation in vascular endothelial cells induces expression of vascular cell adhesion molecule 1 (VCAM-1) and adherence of monocytes, as well as the release of proinflammatory chemokines (13).…”