Changes of GABA A receptor binding and subunit mRNA level in rat brain by infusion of NOS inhibitor

Changes of GABA A receptor binding and subunit mRNA level in rat brain by infusion of NOS inhibitor 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 GABA A receptor binding, and GABA A 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 GABA A 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 ( 3 H)muscimol and ( 3 H)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 ( 35 S)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 ( 3 H)muscimol and ( 3 H)flunitrazepam binding throughout the brain, and alters GABA A receptor subunit mRNA levels in different directions. Chronic inhibition of NO generation has differential effects on the various expressions of GABA A receptor subunits. These suggest the involvement of different regulatory mechanisms for the NO-induced expression of GABA A receptor. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Brain Research Elsevier

Changes of GABA A receptor binding and subunit mRNA level in rat brain by infusion of NOS inhibitor

Brain Research, Volume 952 (2) – Oct 18, 2002

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Publisher
Elsevier
Copyright
Copyright © 2002 Elsevier Science B.V.
ISSN
0006-8993
DOI
10.1016/S0006-8993(02)03248-1
Publisher site
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Abstract

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 GABA A receptor binding, and GABA A 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 GABA A 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 ( 3 H)muscimol and ( 3 H)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 ( 35 S)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 ( 3 H)muscimol and ( 3 H)flunitrazepam binding throughout the brain, and alters GABA A receptor subunit mRNA levels in different directions. Chronic inhibition of NO generation has differential effects on the various expressions of GABA A receptor subunits. These suggest the involvement of different regulatory mechanisms for the NO-induced expression of GABA A receptor.

Journal

Brain ResearchElsevier

Published: Oct 18, 2002

References

  • Effects of nitric oxide-related agents on alcohol narcosis
    Adams, N.L.; Meyer, E.R.; Sewing, B.N.; Cicero, T.J.
  • Influence of nitric oxide synthase inhibition on the development of rapid tolerance to ethanol
    Khanna, J.M.; Morato, G.S.; Chau, A.; Ahah, G.
  • Changes of GABA A receptor binding and subunit mRNA level in rat brain by infusion of subtoxic dose of MK-801
    Kim, H.S.; Choi, H.S.; Lee, S.Y.; Oh, S.
  • Antagonism of ketamine-anesthesia by an inhibitor of nitric oxide synthesis: a pharmacokinetic explanation
    Muller, R.A.; Hunt, R.
  • Activation of protein kinase C by phorbol dibutyrate modulates GABA A receptor binding in rat brain slices
    Oh, S.; Jang, C.G.; Ma, T.; Ho, I.K.
  • Modulation of the GABA A by depressant barbiturates and pregnane steroids
    Peters, J.A.; Kirkness, E.F.; Callachan, H.; Lambert, J.L.; Turner, A.J.
  • Nitric oxide as a neuronal messenger
    Snyder, S.H.; Bredt, D.S.
  • Immediate and long-lasting effects of MK-801 on motor activity, spatial navigation in a swimming pool and EEG in the rats
    Wishaw, I.Q.; Auer, R.N.
  • Role of nitric oxide in learning and memory and in monoamine metabolism in the rat brain
    Yamada, K.; Noda, Y.; Nakayama, S.; Komori, Y.; Sugihara, H.; Hasegawa, T.; Nabeshima, T.

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