Article ID Journal Published Year Pages File Type
2202204 Neurochemistry International 2006 6 Pages PDF
Abstract

Neurotoxic effects of ammonia are mediated by increased accumulation of nitric oxide (NO), which combines with free radicals to form a highly toxic compound, peroxynitrite. Previous experiments in vivo and in vitro have suggested that this phenomenon engages neuron-derived NO and is coupled to changes in the accumulation of cGMP. The present study accounted for the facts that: (i) astrocytes, not neurons are the morphological target of ammonia, and (ii) both NO-dependent, soluble (sGC) and NO-independent, particulate guanylate cyclase (pGC) mediate cGMP production in the cells. Neocortical rat astrocytes were treated for 1 or 24 h with 5 mM ammonium chloride (“ammonia”) and then subjected to: (i) cGMP measurement, and (ii) mRNA and/or protein expression analysis of α1 and β1 subunits of sGC and two pGC forms: pGC-A and pGC-B. Treatment with ammonia for 1 h increased accumulation of cGMP and sGCβ1 mRNA expression, without producing significant changes in the protein expression. This was followed by a decrease of cGMP level at 24 h treatment, associated with a decreased expression of sGCβ1 and sGCα1 mRNA and sGCβ1 protein. Expression of pGC-A and pGC-B mRNA was elevated in ammonia-treated astrocytes after 24 h. Accordingly, increased cGMP accumulation was noted in the presence of a specific sGC inhibitor (ODQ). The results show that ammonia affects cGMP production in astrocytes, and that this may involve not only sGC but also pGC.

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