TY - JOUR
T1 - Calcineurin inhibitors, FK506 and cyclosporin A, suppress the NMDA receptor-mediated potentials and LTP, but not depotentiation in the rat hippocampus
AU - Lu, Y. F.
AU - Tomizawa, K.
AU - Moriwaki, A.
AU - Hayashi, Y.
AU - Tokuda, M.
AU - Itano, T.
AU - Hatase, O.
AU - Matsui, H.
PY - 1996/8/5
Y1 - 1996/8/5
N2 - The effects of FK506, a Ca2+/calmodulin-dependent phosphatase 2B (calcineurin) inhibitor, on the NMDA receptor-mediated potentials and synaptic plasticity were investigated in the CA1 region of the rat hippocampus. Bath application of FK506 (50 μM) produced a 45% inhibition on the NMDA receptor-mediated potentials. FK506 also inhibited the induction of long-term potentiation (LTP), but had no effect on the depotentiation in the CA1 hippocampus. Cyclosporin A (100 μM), another calcineurin inhibitor, mimicked the effects of FK506 on the NMDA responses and synaptic plasticity. These results suggest that FK506 inhibits the activity of NMDA receptors via the involvement of calcineurin. The differential effects of FK506 on LTP and depotentiation may attribute to the partial inhibition on the activity of NMDA receptors and the subsequent attenuation of intracellular Ca2+ increase.
AB - The effects of FK506, a Ca2+/calmodulin-dependent phosphatase 2B (calcineurin) inhibitor, on the NMDA receptor-mediated potentials and synaptic plasticity were investigated in the CA1 region of the rat hippocampus. Bath application of FK506 (50 μM) produced a 45% inhibition on the NMDA receptor-mediated potentials. FK506 also inhibited the induction of long-term potentiation (LTP), but had no effect on the depotentiation in the CA1 hippocampus. Cyclosporin A (100 μM), another calcineurin inhibitor, mimicked the effects of FK506 on the NMDA responses and synaptic plasticity. These results suggest that FK506 inhibits the activity of NMDA receptors via the involvement of calcineurin. The differential effects of FK506 on LTP and depotentiation may attribute to the partial inhibition on the activity of NMDA receptors and the subsequent attenuation of intracellular Ca2+ increase.
KW - Calcineurin
KW - Cyclosporin A
KW - Depotentiation
KW - FK506
KW - Hippocampus
KW - Long-term potentiation
KW - N-Methyl-D-aspartate (NMDA) receptor
KW - Synaptic plasticity
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U2 - 10.1016/0006-8993(96)00568-9
DO - 10.1016/0006-8993(96)00568-9
M3 - Article
C2 - 8874888
AN - SCOPUS:0030570717
VL - 729
SP - 142
EP - 146
JO - Molecular Brain Research
JF - Molecular Brain Research
SN - 0006-8993
IS - 1
ER -