Editing Adenosine (section)

== Pharmacological effects ==
Adenosine is an endogenous purine nucleoside that modulates many physiological processes. Cellular signaling by adenosine occurs through four known adenosine receptor subtypes ([[adenosine A1 receptor|A<sub>1</sub>]], [[adenosine A2A receptor|A<sub>2A</sub>]], [[adenosine A2B receptor|A<sub>2B</sub>]], and [[adenosine A3 receptor|A<sub>3</sub>]]).<ref name="pmid18758473">{{Cite journal | vauthors = Haskó G, Linden J, Cronstein B, Pacher P | title = Adenosine receptors: therapeutic aspects for inflammatory and immune diseases | journal = Nature Reviews. Drug Discovery | volume = 7 | issue = 9 | pages = 759–770 | date = September 2008 | pmid = 18758473 | pmc = 2568887 | doi = 10.1038/nrd2638 }}</ref>

Extracellular adenosine concentrations from normal cells are approximately 300 nM; however, in response to cellular damage (e.g., in inflammatory or [[ischemic]] tissue), these concentrations are quickly elevated (600–1,200 nM). Thus, in regard to stress or injury, the function of adenosine is primarily that of cytoprotection preventing tissue damage during instances of [[hypoxia (medical)|hypoxia]], [[ischemia]], and seizure activity. Activation of A<sub>2A</sub> receptors produces a constellation of responses that in general can be classified as anti-inflammatory.<ref>{{Cite journal | vauthors = Haskó G, Cronstein BN | title = Adenosine: an endogenous regulator of innate immunity | journal = Trends in Immunology | volume = 25 | issue = 1 | pages = 33–39 | date = January 2004 | pmid = 14698282 | doi = 10.1016/j.it.2003.11.003 }}</ref> Enzymatic production of adenosine can be anti-[[Inflammation|inflammatory]] or [[Immunosuppression|immunosuppressive]].<ref name="pmid30513816">{{Cite journal | vauthors = Sek K, Mølck C, Stewart GD, Kats L, Darcy PK, Beavis PA | title = Targeting Adenosine Receptor Signaling in Cancer Immunotherapy | journal = International Journal of Molecular Sciences | volume = 19 | issue = 12 | pages = 3837 | date = December 2018 | pmid = 30513816 | pmc = 6321150 | doi = 10.3390/ijms19123837 | doi-access = free }}</ref><ref name="pmid31878283">{{Cite journal | vauthors = Konen JM, Fradette JJ, Gibbons DL | title = The Good, the Bad and the Unknown of CD38 in the Metabolic Microenvironment and Immune Cell Functionality of Solid Tumors | journal = Cells | volume = 9 | issue = 1 | pages = 52 | date = December 2019 | pmid = 31878283 | pmc = 7016859 | doi = 10.3390/cells9010052 | doi-access = free }}</ref><ref name="pmid23601906">{{Cite journal | vauthors = Antonioli L, Pacher P, Vizi ES, Haskó G | title = CD39 and CD73 in immunity and inflammation | journal = Trends in Molecular Medicine | volume = 19 | issue = 6 | pages = 355–367 | date = June 2013 | pmid = 23601906 | pmc = 3674206 | doi = 10.1016/j.molmed.2013.03.005 }}</ref>

=== Adenosine receptors ===
{{Main|Adenosine receptor}}
All adenosine receptor subtypes (A<sub>1</sub>, A<sub>2A</sub>, A<sub>2B</sub>, and A<sub>3</sub>) are [[G-protein-coupled receptors]]. The four receptor subtypes are further classified based on their ability to either stimulate or inhibit [[adenylate cyclase]] activity. The A<sub>1</sub> receptors couple to G<sub>i/o</sub> and decrease cAMP levels, while the A<sub>2</sub> adenosine receptors couple to G<sub>s</sub>, which stimulates adenylate cyclase activity. In addition, A<sub>1</sub> receptors couple to G<sub>o</sub>, which has been reported to mediate adenosine inhibition of Ca<sup>2+</sup> conductance, whereas A<sub>2B</sub> and A<sub>3</sub> receptors also couple to G<sub>q</sub> and stimulate [[phospholipase]] activity.
Researchers at Cornell University have recently shown adenosine receptors to be key in opening the blood-brain barrier (BBB).
Mice dosed with adenosine have shown increased transport across the BBB of amyloid plaque antibodies and prodrugs associated with Parkinson's disease, Alzheimer's, multiple sclerosis, and cancers of the central nervous system.<ref>{{Cite journal | vauthors = Carman AJ, Mills JH, Krenz A, Kim DG, Bynoe MS | title = Adenosine receptor signaling modulates permeability of the blood-brain barrier | journal = The Journal of Neuroscience | volume = 31 | issue = 37 | pages = 13272–13280 | date = September 2011 | pmid = 21917810 | pmc = 3328085 | doi = 10.1523/JNEUROSCI.3337-11.2011 }}</ref>

=== Ghrelin/growth hormone secretagogue receptor ===
Adenosine is an [[endogenous]] [[agonist]] of the [[Growth hormone secretagogue receptor|ghrelin/growth hormone secretagogue receptor]].<ref name="KordonRobinson2012">{{Cite book | vauthors = Smith RG, Betancourt L, Sun Y | chapter = Role of the Growth Hormone Secretagogue Receptor in the Central Nervous System | veditors = Kordon C, Robinson I, Hanoune J, Dantzer R |title=Brain Somatic Cross-Talk and the Central Control of Metabolism| chapter-url = https://books.google.com/books?id=Ml7vCAAAQBAJ&pg=PA42|year= 2012|publisher=Springer Science & Business Media|isbn=978-3-642-18999-9|pages=42–}}</ref> However, while it is able to increase [[appetite]], unlike other agonists of this receptor, adenosine is unable to induce the secretion of [[growth hormone]] and increase its plasma levels.<ref name="KordonRobinson2012" />

=== Mechanism of action ===
When it is administered intravenously, adenosine causes transient [[heart block]] in the [[atrioventricular node|atrioventricular (AV) node]]. This is mediated via the [[Adenosine A1 receptor|A<sub>1</sub> receptor]], inhibiting adenylyl cyclase, reducing cAMP and so causing cell hyperpolarization by increasing K<sup>+</sup> efflux via [[Potassium channel|inward rectifier K<sup>+</sup> channels]], subsequently inhibiting Ca<sup>2+</sup> current.<ref>{{Cite web|date=2021-03-18|title=Аденозин в косметике - Польза антивозрастной корейской косметики|url=https://kimito.com.ua/adenozin-v-kosmetike/|access-date=2021-03-22|website=KIMITO|language=ru-RU}}</ref><ref>{{Cite book|title = Basic & Clinical Pharmacology |edition=12th| vauthors = Katzung B |publisher = McGraw Hill|year = 2012|page=245|isbn = 978-0-07-176402-5}}</ref> It also causes endothelial-dependent relaxation of smooth muscle as is found inside the artery walls. This causes dilation of the "normal" segments of arteries, i.e. where the [[endothelium]] is not separated from the tunica media by [[atherosclerotic plaque]]. This feature allows physicians to use adenosine to test for blockages in the coronary arteries, by exaggerating the difference between the normal and abnormal segments.

The administration of adenosine also reduces blood flow to coronary arteries past the occlusion. Other coronary arteries dilate when adenosine is administered while the segment past the occlusion is already maximally dilated, which is a process called [[coronary steal]]. This leads to less blood reaching the ischemic tissue, which in turn produces the characteristic chest pain.