[Expression of angiotensin type-2 receptors in rat brain during the cell injury].
The present study examined changes in angiotensin type-2(AT2) receptor mRNA level after global brain ischemia or during glutamate neurotoxicity in cultured cortical cells in rats. The AT2 mRNA level increased by three-fold in both the cortex and hippocampus, which are known to be sensitive to ischemic injury, 3 hr after ischemia. The day 10-14 cortical neurons were exposed to glutamate at a toxic concentration of 100 microM for 15 min. AT2 receptor mRNA was then increased 2-fold after exposure to glutamate, while the maximum increase was observed in a dose-dependent manner 3 hr after glutamate stimulation. AT2 receptor binding also increased 3-12 hr after glutamate exposure. The increase in the mRNA level was antagonized by N-nitro L-arginine methyl-ester, a nitric oxide synthase inhibitor. The hemoglobin, a nitric oxide trap, also inhibited the increase in the mRNA level. These results suggest that the increase in the mRNA level is associated with the nitric oxide synthesis by glutamate exposure. The viability of cortical cells after glutamate stimulation was partially restored by the antisense oligonucleotide for the AT2 receptor. The present results thus suggest the AT2 receptor may in some way be related to one of the processes in cell injury.
Shibata
K
K
Research Laboratory of Biodynamics, School of Medicine, Fukuoka University, Japan.
Makino
I
I
Shibaguchi
H
H
Niwa
M
M
Ohgami
Y
Y
Fujiwara
M
M
Furukawa
T
T
Katsuragi
T
T
D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D018698:Glutamic Acid / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000032:analysis*
D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D009569:Nitric Oxide; D018698:Glutamic Acid