ADORA2A and Iron deficiency anemia: Adenosine has also been implicated: a severe iron deficiency may downregulate the adenosine A1 receptor (A1R) and upregulate the adenosine A2A receptor (A2AR), resulting in a hypoadenosinergic state and an increase of A2ARs that do not form heterodimers with A1Rs, while a milder iron deficiency may only affect A1R.