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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]
Purine metabolites: Nucleotides (e.g., ATP) and nucleosides (e.g., adenosine) that have reached the extracellular space can also serve as danger signals by signaling through purinergic receptors. [30] ATP and adenosine are released in high concentrations after catastrophic disruption of the cell, as occurs in necrotic cell death. [31]
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.
An example of downregulation is the cellular decrease in the expression of a specific receptor in response to its increased activation by a molecule, such as a hormone or neurotransmitter, which reduces the cell's sensitivity to the molecule. This is an example of a locally acting (negative feedback) mechanism.
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.
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.
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]
Adenosine A 3 receptors are G protein-coupled receptors that couple to Gi/Gq and are involved in a variety of intracellular signaling pathways and physiological functions. It mediates a sustained cardioprotective function during cardiac ischemia, it is involved in the inhibition of neutrophil degranulation in neutrophil-mediated tissue injury, it has been implicated in both neuroprotective and ...