The Adenosine 2A Receptor, ME/CFS, POTS and why Caffeine can help

Adenosine normally hits receptors (2A is the important one for today) and promotes sleepiness. Caffeine, however, is an adenosine receptor ANTAGONIST, which means that it hits those same receptors in place of adenosine, and promotes wakefulness instead.
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In both ME/CFS and FMS there is a 40% subgroup, that has a Ad2A (vasoconstriction) decrease. That gene is responsible for preventing orthostatic intolerance (OI / POTS). 70% patients with this gene expression profile have orthostatic intolerance, and 20% without have POTS (it might depend when and how you measure POTS). 

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As with the A1, the A2A receptors are believed to play a role in regulating myocardial oxygen consumption and coronary blood flow.

In addition, A2A receptor can negatively regulate overreactive immune cells, thereby protecting tissues from collateral inflammatory damage.

The A2A receptor is responsible for regulating myocardial blood flow by vasodilating the coronary arteries, which increases blood flow to the myocardium, but may lead to hypotension. Just as in A1 receptors, this normally serves as a protective mechanism, but may be destructive in altered cardiac function.

The A2A receptor is also expressed in the brain, where it has important roles in the regulation of glutamate and dopamine release, making it a potential therapeutic target for the treatment of conditions such as insomnia, pain, depression, drug addiction and Parkinson's disease.