6 262

Cited 29 times in

Differential activation of subtype purinergic receptors modulates Ca(2+) mobilization and COX-2 in human microglia.

Authors
Choi, HB; Hong, SH; Ryu, JK; Kim, SU; McLarnon, JG
Citation
Glia, 43(2):95-103, 2003
Journal Title
Glia
ISSN
0894-14911098-1136
Abstract
We have studied modulation of purinergic receptors (P(2Y) and P(2X) subtypes) on changes in intracellular Ca(2+) [Ca(2+)](i) and expression and production of COX-2 in human microglia. Measurements using Ca(2+)-sensitive spectrofluorometry showed adenosine triphosphate (ATP) to cause rapid transient increases in [Ca(2+)](i). Application of ATP plus the P(2X) antagonist, pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS), or treatment with adenosine diphosphate-beta-S (ADP-beta-S), a selective P(2Y) agonist, led to a considerable prolongation in [Ca(2+)](i) responses compared with ATP. The prolonged time courses were consistent with sustained activation of store-operated channels (SOC) since SKF96365, an inhibitor of SOC, blocked this component of the response. RT-PCR data showed that microglia expressed no COX-2 either constitutively or following treatment of cells with ATP (100 microM for 8 h). However, treatment using ATP plus PPADS or with ADP-beta-S led to marked expression of COX-2. The enhanced COX-2 with ATP plus PPADS treatment was absent in the presence of SKF96365 or using Ca(2+)-free solution. Immunocytochemistry, using a specific anti-COX-2 antibody, also revealed a pattern of purinergic modulation whereby lack of P(2X) activation enhanced the production of COX-2 protein. These results suggest that modulation of subtypes of purinergic receptors regulates COX-2 in human microglia with a link involving SOC-mediated influx of Ca(2+).
MeSH terms
Adenosine Diphosphate/analogs & derivatives*Adenosine Diphosphate/pharmacologyAdenosine Triphosphate/pharmacologyBrain/cytologyBrain/embryologyCalcium/metabolism*Cell Count/methodsCell Size/drug effectsCell SurvivalCells, CulturedCyclooxygenase 2Drug InteractionsvEmbryo, MammalianFluorescent Dyes/metabolismGene Expression/drug effectsHumansImmunohistochemistry/methodsIndoles/metabolismIsoenzymes/geneticsIsoenzymes/metabolism*Membrane ProteinsMicroglia/drug effectsMicroglia/enzymologyMicroglia/metabolism*Platelet Aggregation Inhibitors/pharmacologyProstaglandin-Endoperoxide Synthases/geneticsProstaglandin-Endoperoxide Synthases/metabolism*Purinergic AgonistsPurinergic AntagonistsRNA, Messenger/biosynthesisReceptors, Purinergic/classificationReceptors, Purinergic/metabolism*Reverse Transcriptase Polymerase Chain Reaction/methodsSpectrometry, Fluorescence/instrumentationThionucleotides/pharmacology
DOI
10.1002/glia.10239
PMID
12838502
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Neurology
AJOU Authors
김, 승업
Export
RIS (EndNote)
XLS (Excel)
XML

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse