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An adenosine reuptake inhibitor (AdoRI) is a type of drug which acts as a reuptake inhibitor for the purine nucleoside and neurotransmitter adenosine by blocking the action of one or more of the equilibrative nucleoside transporters (ENTs).
Adenosine is a neuromodulator that is responsible for motor function, mood, memory, and learning. Its main purpose is the coordination of responses to different neurotransmitters. [5] Adenosine plays many important roles in biological systems, for example in the central nervous-, cardiovascular-, hepatic-, renal- and respiratory system.
Caffeine keeps you awake by blocking adenosine receptors. Each type of adenosine receptor has different functions, although with some overlap. [3] For instance, both A 1 receptors and A 2A play roles in the heart, regulating myocardial oxygen consumption and coronary blood flow, while the A 2A receptor also has broader anti-inflammatory effects throughout the body. [4]
Abundant extracellular adenosine can then bind to the A2A receptor resulting in a G s-protein coupled response, resulting in the accumulation of intracellular cAMP, which functions primarily through protein kinase A to upregulate inhibitory cytokines such as transforming growth factor-beta (TGF-β) and inhibitory receptors (i.e., PD-1). [56]
In general, adenosine has an inhibitory effect in the central nervous system (CNS). Caffeine 's stimulatory effects are credited primarily (although not entirely) to its capacity to block adenosine receptors, thereby reducing the inhibitory tonus of adenosine in the CNS.
Caffeine acts as an antagonist of adenosine A 1 and A 2A receptors. Adenosine is a normal neuromodulator that activates adenosine g-protein coupled receptors. The actions of A 1 and A 2A receptors oppose each other but are both inhibited by caffeine due to its function as an antagonist. [8]
Central nervous system fatigue, or central fatigue, is a form of fatigue that is associated with changes in the synaptic concentration of neurotransmitters within the central nervous system (CNS; including the brain and spinal cord) which affects exercise performance and muscle function and cannot be explained by peripheral factors that affect muscle function.
This effect on the A 1 receptor also explains why there is a brief moment of cardiac standstill when adenosine is administered as a rapid IV push during cardiac resuscitation. [citation needed] The rapid infusion causes a momentary myocardial stunning effect. In normal physiological states, this serves as protective mechanisms.