TY - JOUR
T1 - Changes of GABAA receptor binding and subunit mRNA level in rat brain by infusion of NOS inhibitor
AU - Kim, Younghwa
AU - Oh, Seikwan
N1 - Funding Information:
This work was supported by a Korea Research Foundation Grant (KRF-2001-003-F00057).
PY - 2002/10/18
Y1 - 2002/10/18
N2 - In the present study, we have investigated the effects of prolonged inhibition of nitric oxide synthase (NOS) by infusion of NOS inhibitor, L-nitroarginine, to examine the pentobarbital-induced sleep, modulation of GABAA receptor binding, and GABAA receptor subunit mRNA level in rat brain. Pre-treatment with L-nitroarginine 30 min before pentobarbital treatment (60 mg/kg, i.p.) significantly increased the duration of sleep in rats. However, the duration of pentobarbital-induced sleep was shortened by the prolonged infusion of L-nitroarginine into ventricle. We have investigated the effect of NOS inhibitor on GABAA receptor binding characteristics in discrete areas of brain regions by using autoradiographic and in situ hybridization techniques. Rats were infused with L-nitroarginine (10, 100 pmol/10 μl/h, i.c.v.) for 7 days, through pre-implanted cannula by osmotic minipumps. The levels of [3H]muscimol and [3H]flunitrazepam binding were markedly elevated in almost all of brain regions including cortex, caudate putamen, thalamus, hippocampus, and cerebellum. However, there was no change in the level of [35S]TBPS binding. The levels of β2-subunit were elevated in the cortex, brainstem, and cerebellar granule layers. By contrast, the levels of β3-subunit were significantly decreased in the cortex, hippocampus, and cerebellar granule layers in L-nitroarginine-infused rats. Following L-nitroarginine treatment, the levels of α6- and δ-subunits which were strictly localized to the cerebellum, were not changed in the cerebellar granule layer. These results show that the prolonged inhibition of NOS by L-nitroarginine-infusion markedly elevates [3H]muscimol and [3H]flunitrazepam binding throughout the brain, and alters GABAA receptor subunit mRNA levels in different directions. Chronic inhibition of NO generation has differential effects on the various expressions of GABAA receptor subunits. These suggest the involvement of different regulatory mechanisms for the NO-induced expression of GABAA receptor.
AB - In the present study, we have investigated the effects of prolonged inhibition of nitric oxide synthase (NOS) by infusion of NOS inhibitor, L-nitroarginine, to examine the pentobarbital-induced sleep, modulation of GABAA receptor binding, and GABAA receptor subunit mRNA level in rat brain. Pre-treatment with L-nitroarginine 30 min before pentobarbital treatment (60 mg/kg, i.p.) significantly increased the duration of sleep in rats. However, the duration of pentobarbital-induced sleep was shortened by the prolonged infusion of L-nitroarginine into ventricle. We have investigated the effect of NOS inhibitor on GABAA receptor binding characteristics in discrete areas of brain regions by using autoradiographic and in situ hybridization techniques. Rats were infused with L-nitroarginine (10, 100 pmol/10 μl/h, i.c.v.) for 7 days, through pre-implanted cannula by osmotic minipumps. The levels of [3H]muscimol and [3H]flunitrazepam binding were markedly elevated in almost all of brain regions including cortex, caudate putamen, thalamus, hippocampus, and cerebellum. However, there was no change in the level of [35S]TBPS binding. The levels of β2-subunit were elevated in the cortex, brainstem, and cerebellar granule layers. By contrast, the levels of β3-subunit were significantly decreased in the cortex, hippocampus, and cerebellar granule layers in L-nitroarginine-infused rats. Following L-nitroarginine treatment, the levels of α6- and δ-subunits which were strictly localized to the cerebellum, were not changed in the cerebellar granule layer. These results show that the prolonged inhibition of NOS by L-nitroarginine-infusion markedly elevates [3H]muscimol and [3H]flunitrazepam binding throughout the brain, and alters GABAA receptor subunit mRNA levels in different directions. Chronic inhibition of NO generation has differential effects on the various expressions of GABAA receptor subunits. These suggest the involvement of different regulatory mechanisms for the NO-induced expression of GABAA receptor.
KW - Autoradiography
KW - Flunitrazapam
KW - In situ hybridization
KW - Muscimol
KW - Nitric oxide synthase
KW - Osmotic pump
UR - http://www.scopus.com/inward/record.url?scp=0037131097&partnerID=8YFLogxK
U2 - 10.1016/S0006-8993(02)03248-1
DO - 10.1016/S0006-8993(02)03248-1
M3 - Article
C2 - 12376186
AN - SCOPUS:0037131097
VL - 952
SP - 246
EP - 256
JO - Brain Research
JF - Brain Research
SN - 0006-8993
IS - 2
ER -