Chronic Hyperammonemia in Rats Impairs Activation of Soluble Guanylate Cyclase in Neurons and in Lymphocytes: A Putative Peripheral Marker for Neurological Alterations

• Published in: Biochemical and biophysical research communications 1999-04, Vol.257 (2), p.405-409
• Main Authors: Miñana, Marı́a-Dolores, Corbalán, Regina, Montoliu, Carmina, Teng, Che-Ming, Felipo, Vicente
• Format: Article
• Language: English
• Subjects: Ammonia - metabolism; Ammonia - pharmacology; Animals; Biomarkers - analysis; Cells, Cultured; Chronic Disease; Cyclic GMP - metabolism; diet-related diseases; Enzyme Activation - drug effects; Excitatory Amino Acid Antagonists - pharmacology; Glutamic Acid - pharmacology; Guanylate Cyclase - biosynthesis; Hepatic Encephalopathy - etiology; Hepatic Encephalopathy - metabolism; Hepatic Encephalopathy - pathology; human health and safety; human nutrition; Indazoles - antagonists & inhibitors; Indazoles - pharmacology; Lymphocytes - drug effects; Lymphocytes - enzymology; Lymphocytes - metabolism; medicine; Neurons - drug effects; Neurons - enzymology; Neurons - metabolism; Penicillamine - analogs & derivatives; Penicillamine - antagonists & inhibitors; Penicillamine - pharmacology; Rats; Rats, Wistar; S-Nitroso-N-Acetylpenicillamine; Time Factors
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1999.0486

Chronic hyperammonemia impairs the glutamate-nitric oxide-cGMP pathway in rat brainin vivo.The aims of this work were to assess whether hyperammonemia impairs modulation of soluble guanylate cyclase, and to look for a peripheral marker for impairment of this pathway in brain. We activated the pathway at different steps using glutamate, SNAP, or YC-1. In control neurons these compounds increased cGMP by 7.4-, 9.7- and 7.2-fold, respectively. In ammonia-treated neurons formation of cGMP induced by glutamate, SNAP, and YC-1 was reduced by 50%, 56%, and 52%, respectively, indicating that hyperammonemia impairs activation of guanylate cyclase. This enzyme is also present in lymphocytes. Activation of guanylate cyclase by SNAP or YC-1 was impaired in lymphocytes from hyperammonemic rats. These results suggest that determination of the activation of soluble guanylate cyclase in lymphocytes could serve as a peripheral marker for impairment of the neuronal glutamate-nitric oxide-cGMP pathway in brain.