Adenosine A3 receptor-induced CCL2 synthesis in cultured mouse astrocytes.
During neuropathological conditions, high concentrations of adenosine are released, stimulating adenosine receptors in neurons and glial cells. It has recently been shown that stimulation of adenosine receptors in glial cells induces the release of neuroprotective substances such as NGF, S-100beta, and interleukin-6 (IL-6). It has therefore been suggested that glial adenosine receptors are involved in neuroprotection. Since recently neuroprotective effects of the chemokine CCL2 (formerly known as MCP-1) have been reported, we investigated the possible effect of adenosine receptor stimulation on glial CCL2 synthesis. Here we show that stimulation of cultured murine astrocytes with the selective adenosine A3 receptor agonist 2-chloro-N6-(3-iodobenzyl)-N-methyl-5'-carbamoyladenosine (CL-IB-MECA) induced the release of CCL2. Specific ligands for adenosine A1 or A2 receptors did not affect CCL2 release. Furthermore, CL-IB-MECA-induced CCL2 synthesis was inhibited by adenosine A3 receptor antagonists. These results show that stimulation of adenosine A3 receptors in astrocytes induced the release of CCL2, thus supporting the assumption that adenosine receptors in glial cells regulate the synthesis of neuroprotective substances.
Wittendorp
Maria C
MC
Department of Medical Physiology, University of Groningen, Groningen, The Netherlands.
Boddeke
Hendrikus W G M
HW
Biber
Knut
K
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D058907:Adenosine A1 Receptor Agonists; D058908:Adenosine A2 Receptor Agonists; D058909:Adenosine A3 Receptor Agonists; D058918:Adenosine A3 Receptor Antagonists; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects / Q000276:immunology*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D018929:Cell Culture Techniques; D018932:Chemokine CCL2; D051379:Mice; D017628:Microglia / Q000276:immunology / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000276:immunology / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology; D037342:Pertussis Toxin / Q000494:pharmacology; D014176:Protein Biosynthesis; D011506:Proteins / Q000276:immunology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D043684:Receptor, Adenosine A3 / Q000378:metabolism*; D043683:Receptors, Adenosine A2 / Q000378:metabolism
D058907:Adenosine A1 Receptor Agonists; D058908:Adenosine A2 Receptor Agonists; D058909:Adenosine A3 Receptor Agonists; D058918:Adenosine A3 Receptor Antagonists; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D011506:Proteins; D012333:RNA, Messenger; D043682:Receptor, Adenosine A1; D043684:Receptor, Adenosine A3; D043683:Receptors, Adenosine A2; D037342:Pertussis Toxin; D000241:Adenosine; C090034:2-chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide