Chronic hyperammonemia in rats impairs activation of soluble guanylate cyclase in neurons and in lymphocytes: a putative peripheral marker for neurological alterations.
Chronic hyperammonemia impairs the glutamate-nitric oxide-cGMP pathway in rat brain in 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.
Miñana
M D
MD
Instituto de Investigaciones Citologicas, Fundación Valenciana de Investigaciones Biomédicas, Amadeo de Saboya, 4., Valencia, 46010, Spain.
Corbalán
R
R
Montoliu
C
C
Teng
C M
CM
Felipo
V
V
D000641:Ammonia / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002478:Cells, Cultured; D002908:Chronic Disease; D006152:Cyclic GMP / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000096:biosynthesis*; D006501:Hepatic Encephalopathy / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D007191:Indazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D010396:Penicillamine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D026423:S-Nitroso-N-Acetylpenicillamine; D013997:Time Factors
D015415:Biomarkers; D018691:Excitatory Amino Acid Antagonists; D007191:Indazoles; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole; D018698:Glutamic Acid; D000641:Ammonia; D026423:S-Nitroso-N-Acetylpenicillamine; D006162:Guanylate Cyclase; D010396:Penicillamine; D006152:Cyclic GMP