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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. [34]
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).
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.
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]
In 1965, the effects of caffeine on mammalian atrial muscle was documented by De Gubareffand Sleator. Then 5 years later, the effects of adenosine and adenine nucleotides on the cAMP in the guinea pig brain was described by Sattin and Rall. [1] In 1980, methylxanthines caffeine and theophylline were observed in mice by Fredholm and others.
An adenosine receptor antagonist is a drug which acts as an antagonist of one or more of the adenosine receptors. [1] The best known are xanthines and their derivatives (natural: caffeine, [2] theophylline, [3] and theobromine; and synthetic: PSB-1901 [4]), but there are also non-xanthine representatives (e.g. ISAM-140, [5] ISAM-R316, [6] etrumadenant, [7] and AZD-4635 [8])
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]
P2Y 12 is a chemoreceptor for adenosine diphosphate (ADP) [5] [6] that belongs to the G i class of a group of G protein-coupled (GPCR) purinergic receptors. [7] This P2Y receptor family has several receptor subtypes with different pharmacological selectivity, which overlaps in some cases, for various adenosine and uridine nucleotides.