Adenosine A2A-receptor stimulation inhibits lipopolysaccharide-induced interleukin-18 production in monocytes.
Adenosine inhibited interleukin (IL)-18 production in lipopolysaccharide (LPS)-stimulated monocytes. The action of adenosine was antagonized by an adenosine A2A-receptor (A2AR) antagonist and was mimicked by an A2AR agonist, suggesting that the stimulation of A2AR may be involved in the actions of adenosine. On the other hand, the stimulation of A1R and A3R inhibited the actions of A2AR stimulation, whereas the stimulation of A2BR had no effect on them. Activation of A2AR is known to increase cyclic adenosine monophosphate (cAMP) levels and to activate protein kinase A (PKA). A PKA inhibitor prevented the actions of A2AR stimulation, indicating that the action mechanism of A2AR stimulation may be via the activation of the cAMP/PKA pathway.
Takahashi
Hideo Kohka
HK
Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama, Japan.
Kanke
Toru
T
Liu
Keyue
K
Yoshino
Tadashi
T
Sendo
Toshiaki
T
Tanaka
Noriaki
N
Nishibori
Masahiro
M
D000241:Adenosine / Q000008:administration & dosage / Q000494:pharmacology*; D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D000242:Cyclic AMP / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D020128:Inhibitory Concentration 50; D020382:Interleukin-18 / Q000096:biosynthesis*; D008070:Lipopolysaccharides; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000378:metabolism*
D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D020382:Interleukin-18; D008070:Lipopolysaccharides; D043705:Receptor, Adenosine A2A; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000241:Adenosine