P2X7 receptor mediated phosphorylation of p38MAP kinase in the hippocampus.
This study was designed to explore the effect of P2X7 receptor (P2X7R) activation on the expression of p38 MAP kinase (p38 MAPK) enzyme in hippocampal slices of wild-type (WT) and P2X7R(-/-) mice using the Western blot technique and to clarify its role in P2X7 receptor mediated [(3)H]glutamate release. ATP (1 mM) and the P2X7R agonist BzATP (100 microM) significantly increased p38 MAPK phosphorylation in WT mice, and these effects were absent in the hippocampal slices of P2X7R(-/-) mice. Both ATP- and BzATP-induced p38 MAPK phosphorylations were sensitive to the p38 MAP kinase inhibitor, SB203580 (1 microM). ATP elicited [(3)H]glutamate release from hippocampal slices, which was significantly attenuated by SB203580 (1 microM) but not by the extracellular signal-regulated kinase (ERK1/2) inhibitor, PD098095 (10 microM). Consequently, we suggest that P2X7Rs and p38 MAPK are involved in the stimulatory effect of ATP on glutamate release in the hippocampal slices of WT mice.
Papp
Lilla
L
Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, H-1450 Budapest, Hungary. lillapapp@gmail.com
Vizi
E Sylvester
ES
Sperlágh
Beáta
B
D000818:Animals; D015153:Blotting, Western; D005419:Flavonoids / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000201:enzymology*; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D058910:Purinergic P2 Receptor Agonists; D011725:Pyridines / Q000494:pharmacology; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000502:physiology*; D058486:Receptors, Purinergic P2X7; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D005419:Flavonoids; D007093:Imidazoles; C546469:P2rx7 protein, mouse; D047428:Protein Kinase Inhibitors; D058910:Purinergic P2 Receptor Agonists; D011725:Pyridines; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D018698:Glutamic Acid; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one