Sandcastle replied: "Caffeine acts through multiple mechanisms involving both action on receptors and channels on the cell membrane, as well as intracellular action on calcium and cAMP pathways. By virtue of its purine structure it can act on some of the same targets as adenosine related nucleosides and nucleotides, like the cell surface P1 GPCRs for adenosine, as well as the intracellular Ryanodine receptor (RyR) which is the physiological target of cADPR (cyclic ADP-ribose), and cAMP-phosphodiesterase (cAMP-PDE). Although the action is agonistic in some cases, it is antagonistic in others. Physiologically, however, caffeine action is unlikely due to increased RyR opening, as it requires plasma concentration above lethal dosage. The action is most likely through adenosine receptors. Like alcohol, nicotine, and antidepressants, caffeine readily crosses the blood brain barrier. Once in the brain, the principal mode of action of caffeine is as an antagonist of adenosine receptors found in the brain.[39] The caffeine molecule is structurally similar to adenosine, and binds to adenosine receptors on the surface of cells without activating them (an "antagonist" mechanism of action). Therefore, caffeine acts as a competitive inhibitor. The reduction in adenosine activity results in increased activity of the neurotransmitter dopamine, largely accounting for the stimulatory effects of caffeine. Caffeine can also increase levels of epinephrine/adrenaline,[40] possibly via a different mechanism. Acute usage of caffeine also increases levels of serotonin, causing positive changes in mood.[41] Caffeine is also a known competitive inhibitor of the enzyme cAMP-phosphodiesterase (cAMP-PDE), which converts cyclic AMP (cAMP) in cells to its noncyclic form, allowing cAMP to build up in cells. Cyclic AMP participates in activation of Protein Kinase A (PKA) to begin the phosphorylation of specific enzymes used in glucose synthesis. By blocking its removal caffeine intensifies and prolongs the effects of epinephrine and epinephrine-like drugs such as amphetamine, methamphetamine, or methylphenidate. Increased concentrations of cAMP in parietal cells causes an increased activation of protein kinase A (PKA) which in turn increases activation of H+/K+ ATPase, resulting finally in increased gastric acid secretion by the cell. Caffeine (and theophylline) can freely diffuse into cells and causes intracellular calcium release (independent of extracellular calcium) from the calcium stores in the endoplasmic reticulum(ER). This release is only partially blocked by Ryanodine receptor blockade with ryanodine, dantrolene, ruthenium red, and procaine (thus may involve ryanodine receptor and probably some additional calcium channels), but completely abolished after calcium depletion of ER by SERCA inhibitors like Thapsigargin (TG) or cyclopiazonic acid (CPA).[42] The action of caffeine on the ryanodine receptor may depend on both cytosolic and the luminal ER concentrations of Ca2+. At low millimolar concentration of caffeine, the RyR channel open probability (Po) is significantly increased mostly due to a shortening of the lifetime of the closed state. At concentrations >5 mM, caffeine opens RyRs even at picomolar cytosolic Ca2+ and dramatically increases the open time of the channel so that the calcium release is stronger than even an action potential can generate. This mode of action of caffeine is probably due to mimicking the action of the physiologic metabolite of NAD called cADPR (cyclic ADP ribose) which has a similar potentiating action on Ryanodine receptors. Caffeine may also directly inhibit delayed rectifier and A-type K+ currents and activate plasmalemmal Ca2+ influx in certain vertebrate and invertebrate neurons. The metabolites of caffeine contribute to caffeine's effects. Theobromine is a vasodilator that increases the amount of oxygen and nutrient flow to the brain and muscles. Theophylline, the second of the three primary metabolites, acts as a smooth muscle relaxant that chiefly affects bronchioles and acts as a chronotrope and inotrope that increases heart rate and efficiency. The third metabolic derivative, paraxanthine, is responsible for an increase in the lipolysis process, which releases glycerol and fatty acids into the blood to be used as a source of fuel by the muscles.[43]"