UDP facilitates microglial phagocytosis through P2Y6 receptors.
Microglia engage in the clearance of dead cells or dangerous debris. When neighboring cells are injured, the cells release or leak ATP into extracellular space and microglia rapidly move toward or extend a process to the nucleotides as chemotaxis through P2Y12 receptors. In the meanwhile, microglia express the metabotropic P2Y6 receptors, the activation of which by uridine 5'-diphosphate (UDP) triggers microglial phagocytosis in a concentration-dependent fashion. UDP/UTP was leaked when hippocampal neurons were damaged by kainic acid in vivo and in vitro. Systemic administration of kainic acid in rats resulted in neuronal cell death in the hippocampal CA1 and CA3 regions, where increases in mRNA for P2Y6 receptors in activated microglia. Thus, the P2Y6 receptor is upregulated when neurons are damaged, and would function as a sensor for phagocytosis by sensing diffusible UDP signals.
Inoue
Kazuhide
K
Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi Higashi, Fukuoka 812-8582 Japan. kazuinouejp@ybb.ne.jp
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D018690:Excitatory Amino Acid Agonists / Q000009:adverse effects / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D007608:Kainic Acid / Q000009:adverse effects / Q000494:pharmacology; D017628:Microglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects / Q000502:physiology; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058925:Receptors, Purinergic P2Y12; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D014530:Uridine Diphosphate / Q000378:metabolism*
D018690:Excitatory Amino Acid Agonists; C548576:P2RY12 protein, human; C553058:P2ry12 protein, rat; D018048:Receptors, Purinergic P2; D058925:Receptors, Purinergic P2Y12; C099845:purinoceptor P2Y6; D014530:Uridine Diphosphate; D000255:Adenosine Triphosphate; D007608:Kainic Acid