title: Adenosine A3 receptor is involved in ADP-induced microglial process extension and migration.
abstract: The extension of microglial processes toward injured sites in the brain is triggered by the stimulation of the purinergic receptor P2Y(12) by extracellular ATP. We recently showed that P2Y(12) stimulation by ATP induces microglial process extension in collagen gels. In the present study, we found that a P2Y(12) agonist, 2-methylthio-ADP (2MeSADP), failed to induce the process extension of microglia in collagen gels and that co-stimulation with adenosine, a phosphohydrolytic derivative of ATP, and 2MeSADP restored the chemotactic process extension. An adenosine A3 receptor (A3R)-selective agonist restored the chemotactic process extension, but other receptor subtype agonists did not. The removal of adenosine by adenosine deaminase and the blocking of A3R by an A3R-selective antagonist inhibited ADP-induced process extension. The A3R antagonist inhibited ADP-induced microglial migration, and an A3R agonist promoted 2MeSADP-stimulated migration. ADP and the A3R agonist activated Jun N-terminal kinase in microglia, and a Jun N-terminal kinase inhibitor inhibited the ADP-induced process extension. An RT-PCR analysis showed that A1R and A3R were expressed by microglia sorted from adult rat brains and that the A2AR expression level was very low. These results suggested that A3R signaling may be involved in the ADP-induced process extension and migration of microglia.
authors.affiliation: Department of Neurochemistry, National Institute of Neuroscience, 4-1-1 Ogawahigashi Kodaira, Tokyo 187-8502, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Ohsawa
authors.forename: Tomomi
authors.initials: T
authors.lastname: Sanagi
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Eri
authors.initials: E
authors.lastname: Suzuki
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Inoue
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kohsaka
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D058909:Adenosine A3 Receptor Agonists / Q000494:pharmacology; D058892:Adenosine Deaminase Inhibitors / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D003094:Collagen; D005434:Flow Cytometry; D007202:Indicators and Reagents; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology; D017628:Microglia / Q000187:drug effects*; D058912:Purinergic P2Y Receptor Agonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D043682:Receptor, Adenosine A1 / Q000096:biosynthesis; D043684:Receptor, Adenosine A3 / Q000187:drug effects / Q000502:physiology*; D058925:Receptors, Purinergic P2Y12 / Q000187:drug effects; D013873:Thionucleotides / Q000494:pharmacology
chemical_list: D058909:Adenosine A3 Receptor Agonists; D058892:Adenosine Deaminase Inhibitors; D007202:Indicators and Reagents; D058912:Purinergic P2Y Receptor Agonists; D043682:Receptor, Adenosine A1; D043684:Receptor, Adenosine A3; D058925:Receptors, Purinergic P2Y12; D013873:Thionucleotides; C002480:methylthio-ADP; D000244:Adenosine Diphosphate; D003094:Collagen; D048031:JNK Mitogen-Activated Protein Kinases; D000241:Adenosine