THE INCREASE IN ANGIOTENSIN TYPE-2 RECEPTOR MESSENGER-RNA LEVEL BY GLUTAMATE STIMULATION IN CULTURED RAT CORTICAL-CELLS

The changes in the angiotensin type-2 (AT2) receptor mRNA level during glutamate neurotoxicity in cultured rat cortical cells are examined t o assess the possible involvement of An. receptor in cell injury. The day 10-14 cortical neurons were exposed to glutamate at a toxic concen tration of 100 mu M for 15 min. The viability of the culture was reduc ed by 60% after 24 h. AT2 receptor mRNA was then increased 2-fold afte r exposure to glutamate, while the maximum increase was observed in a dose-dependent manner (50-1000 mu M) 3 h after glutamate stimulation. AT2 receptor binding also increased 3-12 h after glutamate exposure. T he results suggest that the increase in the An receptor preceded to so me extent the insult of the cell after exposure. The increase in the m RNA level was suppressed by MK-801, N-methyl-D-aspartate (NMDA) recept or antagonist, thus indicating the possible involvement of NMDA recept or. The increase in the mRNA level was also antagonized by N-nitro L-a rginine methyl-ester, a nitric oxide synthase inhibitor. The hemoglobi n, a nitric oxide trap, inhibited the increase in the mRNA level. Thes e results suggest that the increase in the mRNA level is associated wi th the nitric oxide synthesis by glutamate exposure. The viability of cortical cells after glutamate stimulation was partially restored by t he AT2 receptor antagonist and by the antisense oligonucleotide for th e An receptor. The present results thus suggest that the AT2 receptor may in some way be related to one of the processes in cell injury caus ed by glutamate. (C) 1998 Elsevier Science B.V. All rights reserved.