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Hyperammonemia alters glycinergic neurotransmission and modulation of the glutamate-nitric oxide-cGMP pathway by extracellular glycine in cerebellum in vivo.
J Neurochem. 2016 05; 137(4):539-48.JN

Abstract

The glutamate-nitric oxide (NO)-cGMP pathway modulates some forms of learning. How glycine modulates this pathway is unclear. Glycine could modulate the pathway biphasically, enhancing its function through NMDA receptor activation or reducing it through glycine receptor activation. Chronic hyperammonemia impairs the glutamate-NO-cGMP pathway in the cerebellum and induces cognitive impairment. The possible alterations in hyperammonemia of glycinergic neurotransmission and of glutamate-NO-cGMP pathway modulation by glycine remain unknown. The aims were to assess, by in vivo microdialysis in cerebellum: (i) the effects of different glycine concentrations, administered through the microdialysis probe, on the glutamate-NO-cGMP pathway function; (ii) the effects of tonic glycine receptors activation on the pathway function, by blocking them with strychnine; (iii) whether hyperammonemia alters the pathway modulation by glycine; (iv) and whether hyperammonemia alters extracellular glycine concentration and/or glycine receptor membrane expression. In control rats, low glycine levels reduce the pathway function, likely by activating glycine receptors, while 20 μM glycine enhances the pathway function, likely by enhancing NMDA receptor activation. In hyperammonemic rats, glycine did not reduce the pathway function, but enhanced it when administered at 1-20 μM. Hyperammonemia reduces extracellular glycine concentration by approximately 50% and glycine receptor membrane expression. However, tonic glycine receptor activation seems to be enhanced in hyperammonemic rats, as indicated by the larger increase in extracellular cGMP induced by strychnine. These data show that glycine modulates the glutamate-NO-cGMP pathway biphasically and that hyperammonemia strongly alters glycinergic neurotransmission and modulation by glycine of the glutamate-NO-cGMP pathway. These alterations may contribute to the cerebellar aspects of cognitive alterations in hyperammonemia. The findings reported in this study show that hyperammonemia alters glycinergic neurotransmission and the glutamate-NO-cGMP pathway modulation by glycine. In control rats, low glycine levels reduced the pathway function, likely by activating glycine receptors, while 20 μM glycine enhanced the pathway, likely by enhancing NMDA receptor activation. In hyperammonemic rats, glycine (administered at 1-20 μM) enhances the pathway, likely by activating NMDA receptors.

Authors+Show Affiliations

Laboratorio de Neurobiología, Centro Investigación Príncipe Felipe de Valencia, Valencia, Spain.Laboratorio de Neurobiología, Centro Investigación Príncipe Felipe de Valencia, Valencia, Spain.Laboratorio de Neurobiología, Centro Investigación Príncipe Felipe de Valencia, Valencia, Spain.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26875688

Citation

Cabrera-Pastor, Andrea, et al. "Hyperammonemia Alters Glycinergic Neurotransmission and Modulation of the Glutamate-nitric oxide-cGMP Pathway By Extracellular Glycine in Cerebellum in Vivo." Journal of Neurochemistry, vol. 137, no. 4, 2016, pp. 539-48.
Cabrera-Pastor A, Taoro-Gonzalez L, Felipo V. Hyperammonemia alters glycinergic neurotransmission and modulation of the glutamate-nitric oxide-cGMP pathway by extracellular glycine in cerebellum in vivo. J Neurochem. 2016;137(4):539-48.
Cabrera-Pastor, A., Taoro-Gonzalez, L., & Felipo, V. (2016). Hyperammonemia alters glycinergic neurotransmission and modulation of the glutamate-nitric oxide-cGMP pathway by extracellular glycine in cerebellum in vivo. Journal of Neurochemistry, 137(4), 539-48. https://doi.org/10.1111/jnc.13579
Cabrera-Pastor A, Taoro-Gonzalez L, Felipo V. Hyperammonemia Alters Glycinergic Neurotransmission and Modulation of the Glutamate-nitric oxide-cGMP Pathway By Extracellular Glycine in Cerebellum in Vivo. J Neurochem. 2016;137(4):539-48. PubMed PMID: 26875688.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hyperammonemia alters glycinergic neurotransmission and modulation of the glutamate-nitric oxide-cGMP pathway by extracellular glycine in cerebellum in vivo. AU - Cabrera-Pastor,Andrea, AU - Taoro-Gonzalez,Lucas, AU - Felipo,Vicente, Y1 - 2016/03/02/ PY - 2015/11/16/received PY - 2016/02/01/revised PY - 2016/02/03/accepted PY - 2016/2/16/entrez PY - 2016/2/16/pubmed PY - 2017/6/6/medline KW - NMDA receptors KW - cGMP KW - glycine receptors KW - glycinergic neurotrans-mission KW - hyperammonemia KW - nitric oxide SP - 539 EP - 48 JF - Journal of neurochemistry JO - J Neurochem VL - 137 IS - 4 N2 - The glutamate-nitric oxide (NO)-cGMP pathway modulates some forms of learning. How glycine modulates this pathway is unclear. Glycine could modulate the pathway biphasically, enhancing its function through NMDA receptor activation or reducing it through glycine receptor activation. Chronic hyperammonemia impairs the glutamate-NO-cGMP pathway in the cerebellum and induces cognitive impairment. The possible alterations in hyperammonemia of glycinergic neurotransmission and of glutamate-NO-cGMP pathway modulation by glycine remain unknown. The aims were to assess, by in vivo microdialysis in cerebellum: (i) the effects of different glycine concentrations, administered through the microdialysis probe, on the glutamate-NO-cGMP pathway function; (ii) the effects of tonic glycine receptors activation on the pathway function, by blocking them with strychnine; (iii) whether hyperammonemia alters the pathway modulation by glycine; (iv) and whether hyperammonemia alters extracellular glycine concentration and/or glycine receptor membrane expression. In control rats, low glycine levels reduce the pathway function, likely by activating glycine receptors, while 20 μM glycine enhances the pathway function, likely by enhancing NMDA receptor activation. In hyperammonemic rats, glycine did not reduce the pathway function, but enhanced it when administered at 1-20 μM. Hyperammonemia reduces extracellular glycine concentration by approximately 50% and glycine receptor membrane expression. However, tonic glycine receptor activation seems to be enhanced in hyperammonemic rats, as indicated by the larger increase in extracellular cGMP induced by strychnine. These data show that glycine modulates the glutamate-NO-cGMP pathway biphasically and that hyperammonemia strongly alters glycinergic neurotransmission and modulation by glycine of the glutamate-NO-cGMP pathway. These alterations may contribute to the cerebellar aspects of cognitive alterations in hyperammonemia. The findings reported in this study show that hyperammonemia alters glycinergic neurotransmission and the glutamate-NO-cGMP pathway modulation by glycine. In control rats, low glycine levels reduced the pathway function, likely by activating glycine receptors, while 20 μM glycine enhanced the pathway, likely by enhancing NMDA receptor activation. In hyperammonemic rats, glycine (administered at 1-20 μM) enhances the pathway, likely by activating NMDA receptors. SN - 1471-4159 UR - https://www.unboundmedicine.com/medline/citation/26875688/Hyperammonemia_alters_glycinergic_neurotransmission_and_modulation_of_the_glutamate_nitric_oxide_cGMP_pathway_by_extracellular_glycine_in_cerebellum_in_vivo_ L2 - https://doi.org/10.1111/jnc.13579 DB - PRIME DP - Unbound Medicine ER -