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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]
The activation of the adenosine A1 receptor is required for osteoclast differentiation and function, whereas the activation of the adenosine A2A receptor inhibits osteoclast function. The other three adenosine receptors are involved in bone formation.
Adenosine is a key factor in regulating the body's sleep-wake cycle. [39] Adenosine levels rise during periods of wakefulness and lowers during sleep. Higher adenosine levels correlate with a stronger feeling of sleepiness, also known as sleep drive or sleep pressure. [40]
P1 receptors are preferentially activated by adenosine and P2Y receptors are preferentially more activated by ATP. P1 and P2Y receptors are known to be widely distributed in the brain, heart, kidneys, and adipose tissue. Xanthines (e.g. caffeine) specifically block adenosine receptors, and are known to induce a stimulating effect to one's behavior.
The ATP is subsequently converted to adenosine by ecto-5′-nucleotidase. [10] Adenosine constricts the afferent arteriole by binding with high affinity to the A 1 receptors [11] [12] a G i /G o. Adenosine binds with much lower affinity to A 2A and A 2B [13] receptors causing dilation of efferent arterioles. [12]
Adenosinergic means "working on adenosine". An adenosinergic agent (or drug) is a chemical which functions to directly modulate the adenosine system in the body or brain. Examples include adenosine receptor agonists, adenosine receptor antagonists (such as caffeine), and adenosine reuptake inhibitors.
The actions of the A 2A receptor are complicated by the fact that a variety of functional heteromers composed of a mixture of A 2A subunits with subunits from other unrelated G-protein coupled receptors have been found in the brain, adding a further degree of complexity to the role of adenosine in modulation of neuronal activity.
A 1 receptors are implicated in sleep promotion by inhibiting wake-promoting cholinergic neurons in the basal forebrain. [6] A 1 receptors are also present in smooth muscle throughout the vascular system. [7] The adenosine A 1 receptor has been found to be ubiquitous throughout the entire body. [citation needed]