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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. This reduction in adenosine activity leads to increased activity of the neurotransmitters dopamine and glutamate . [ 35 ]
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).
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]
It also causes a negative dromotropic effect through the inhibition of AV-nodal conduction. [20] From the 1980s onwards, these effects of adenosine have been used in the treatment of patients with supraventricular tachycardia. [21] The regulation of vascular tone in the endothelium of blood vessels is mediated by purinergic signalling.
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.
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.
Gamma-aminobutyric acid (GABA) has an inhibitory effect on brain and spinal cord activity. [17] GABA is an amino acid that is the primary inhibitory neurotransmitter for the central nervous system (CNS). It reduces neuronal excitability by inhibiting nerve transmission.
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]