title: The role of adenosine signaling in sickle cell therapeutics.
abstract: Data suggest a role for adenosine signaling in the pathogenesis of sickle cell disease (SCD). Signaling through the adenosine A2A receptor (A2AR) has demonstrated beneficial effects. Activation of A2ARs decreases inflammation with SCD by blocking activation of invariant natural killer T cells. Decreased inflammation may reduce the severity of vasoocclusive crises. Adenosine signaling through the adenosine A2B receptor (A2BR) may be detrimental in SCD. Whether adenosine signaling predominantly occurs through A2ARs or A2BRs may depend on differing levels of adenosine and disease state (steady state versus crisis). There may be opportunities to develop novel therapeutic approaches targeting A2ARs and/or A2BRs for patients with SCD.
authors.affiliation: Blood Research Institute, BloodCenter of Wisconsin, 8733 Watertown Plank Road, Milwaukee, WI 53226, USA; Department of Medicine, Medical College of Wisconsin, 9200 West Wisconsin Avenue, Milwaukee, WI 53226, USA. Electronic address: joshua.field@bcw.edu.
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Field
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Division of Pediatric Hematology and Oncology, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Nathan
authors.affiliation: Inflammation Biology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, San Diego, CA 92037, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Linden
mesh_terms: D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use; D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000755:Anemia, Sickle Cell / Q000188:drug therapy / Q000378:metabolism*; D000818:Animals; D006801:Humans; D011687:Purines / Q000494:pharmacology / Q000627:therapeutic use; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D043704:Receptor, Adenosine A2B / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; C496145:N-(4-acetylphenyl)-2-(4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3-dipropyl-1H-purin-8-yl)phenoxy)acetamide; D011687:Purines; D011720:Pyrazoles; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; C430916:regadenoson
keywords: Adenosine; Adenosine A(2A) receptor; Adenosine A(2B) receptor; NKT cells; Sickle cell disease