Adenosine Stereotypes

Adenosine plays a huge role in the way we feel and behave on any given basis. Adenosine is generated by intracellular and extracellular factors by the breakup of adenine nucleotides. Adenosine is formed predominantly by dephosphorylation of adenosine monophosphate (AMP), catalyzed by intracellular cytosolic enzyme 5′-nucleotidase. ATP is released from neurons as neurotransmitters when the cell membrane is subjected to mechanical stress. All adenosine receptor subtypes (A1, A2A, A2B, and A3) are G-protein-coupled receptors. The four receptor subtypes are further classified based on their ability to either stimulate or inhibit adenylate cyclase activity. The A1 receptors couple to Gi/o and decreases cAMP levels, while the A2 adenosine receptors couple to Gs, which stimulates adenylate cyclase activity. In addition, A1 receptors couple to Go, which has been reported to mediate adenosine inhibition of Ca2+ conductance, whereas A2B and A3 receptors also couple to Gq and stimulate phospholipase activity.
The stimulant effect of coffee comes from the way it acts on the adenosine receptors in the neural membrane. When adenosine binds to receptors, neural activity slows down, making you feel tired. Caffeine acts as an adenosine-receptor agonist, this means that it binds to the same receptors, but without causing slowed neural activity. The
Adenosine, exerts effects on neurons and glial cells of all brain areas. As a direct consequence, caffeine, when acting as an AR antagonist, is doing the opposite of activation of adenosine receptors. Besides AR antagonism, xanthines, including caffeine, have other biological actions, they inhibit phosphodiesterases (PDEs) (examples, PDE1, PDE4, PDE5), promote calcium release from intracellular storage, and interfere with GABA-A receptors (are the major inhibitory neurotransmitter receptors in mammalian