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Brain regional alterations in the modulation of the glutamate-nitric oxide-cGMP pathway in liver cirrhosis. Role of hyperammonemia and cell types involved.
Neurochem Int. 2006 May-Jun; 48(6-7):472-7.NI

Abstract

Hepatic encephalopathy is a complex neuropsychiatric syndrome present in patients with liver disease that includes impaired intellectual function and alterations in personality and neuromuscular coordination. Hyperammonemia and liver failure result in altered glutamatergic neurotransmission, which contributes to hepatic encephalopathy. Alterations in the function of the glutamate-nitric oxide-cGMP pathway may be responsible for some of the neurological alterations found in hepatic encephalopathy. The function of this pathway is altered in brain from patients died with liver cirrhosis and one altered step of the pathway is the activation of soluble guanylate cyclase by nitric oxide, which is increased in cerebral cortex and reduced in cerebellum from these patients. Portacaval anastomosis and bile duct ligation plus hyperammonemia in rats reproduce the alterations in the activation of soluble guanylate cyclase by NO both in cerebellum and cerebral cortex. We assessed whether hyperammonemia is responsible for the region-selective alterations in guanylate cyclase modulation in liver cirrhosis and whether the alteration occurs in neurons or in astrocytes. Activation of guanylate cyclase by nitric oxide is lower in cerebellar neurons exposed to ammonia (1.5-fold) than in control neurons (3.3-fold). The activation of guanylate cyclase by nitric oxide is higher in cortical neurons exposed to ammonia (8.7-fold) than in control neurons (5.5-fold). The activation is not affected in cerebellar or cortical astrocytes. These findings indicate that hyperammonemia is responsible for the differential alterations in the modulation of soluble guanylate cyclase by nitric oxide in cerebellum and cerebral cortex of cirrhotic patients. Moreover, under the conditions used, the alterations occur selectively in neurons and not in astrocytes.

Authors+Show Affiliations

Laboratory of Neurobiology, Centro de Investigacion Principe Felipe, Fundación de la Comunidad Valenciana Centro de Investigacion Principe Felipe, Valencia, Spain.No affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

16517021

Citation

Rodrigo, Regina, and Vicente Felipo. "Brain Regional Alterations in the Modulation of the Glutamate-nitric oxide-cGMP Pathway in Liver Cirrhosis. Role of Hyperammonemia and Cell Types Involved." Neurochemistry International, vol. 48, no. 6-7, 2006, pp. 472-7.
Rodrigo R, Felipo V. Brain regional alterations in the modulation of the glutamate-nitric oxide-cGMP pathway in liver cirrhosis. Role of hyperammonemia and cell types involved. Neurochem Int. 2006;48(6-7):472-7.
Rodrigo, R., & Felipo, V. (2006). Brain regional alterations in the modulation of the glutamate-nitric oxide-cGMP pathway in liver cirrhosis. Role of hyperammonemia and cell types involved. Neurochemistry International, 48(6-7), 472-7.
Rodrigo R, Felipo V. Brain Regional Alterations in the Modulation of the Glutamate-nitric oxide-cGMP Pathway in Liver Cirrhosis. Role of Hyperammonemia and Cell Types Involved. Neurochem Int. 2006 May-Jun;48(6-7):472-7. PubMed PMID: 16517021.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Brain regional alterations in the modulation of the glutamate-nitric oxide-cGMP pathway in liver cirrhosis. Role of hyperammonemia and cell types involved. AU - Rodrigo,Regina, AU - Felipo,Vicente, Y1 - 2006/03/06/ PY - 2005/10/14/received PY - 2005/10/28/revised PY - 2005/10/31/accepted PY - 2006/3/7/pubmed PY - 2006/6/10/medline PY - 2006/3/7/entrez SP - 472 EP - 7 JF - Neurochemistry international JO - Neurochem Int VL - 48 IS - 6-7 N2 - Hepatic encephalopathy is a complex neuropsychiatric syndrome present in patients with liver disease that includes impaired intellectual function and alterations in personality and neuromuscular coordination. Hyperammonemia and liver failure result in altered glutamatergic neurotransmission, which contributes to hepatic encephalopathy. Alterations in the function of the glutamate-nitric oxide-cGMP pathway may be responsible for some of the neurological alterations found in hepatic encephalopathy. The function of this pathway is altered in brain from patients died with liver cirrhosis and one altered step of the pathway is the activation of soluble guanylate cyclase by nitric oxide, which is increased in cerebral cortex and reduced in cerebellum from these patients. Portacaval anastomosis and bile duct ligation plus hyperammonemia in rats reproduce the alterations in the activation of soluble guanylate cyclase by NO both in cerebellum and cerebral cortex. We assessed whether hyperammonemia is responsible for the region-selective alterations in guanylate cyclase modulation in liver cirrhosis and whether the alteration occurs in neurons or in astrocytes. Activation of guanylate cyclase by nitric oxide is lower in cerebellar neurons exposed to ammonia (1.5-fold) than in control neurons (3.3-fold). The activation of guanylate cyclase by nitric oxide is higher in cortical neurons exposed to ammonia (8.7-fold) than in control neurons (5.5-fold). The activation is not affected in cerebellar or cortical astrocytes. These findings indicate that hyperammonemia is responsible for the differential alterations in the modulation of soluble guanylate cyclase by nitric oxide in cerebellum and cerebral cortex of cirrhotic patients. Moreover, under the conditions used, the alterations occur selectively in neurons and not in astrocytes. SN - 0197-0186 UR - https://www.unboundmedicine.com/medline/citation/16517021/Brain_regional_alterations_in_the_modulation_of_the_glutamate_nitric_oxide_cGMP_pathway_in_liver_cirrhosis__Role_of_hyperammonemia_and_cell_types_involved_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-0186(06)00040-4 DB - PRIME DP - Unbound Medicine ER -