Ammonia

The glial glutamate transporter in hyperammonemia and hepatic encephalopathy: Relation to energy metabolism and glutamatergic neurotransmission

“…Ammonia brain levels correlate well with neuronal activity: a reduction in functional activity is associated with decreased ammonia levels, while elevated ammonia levels are observed with intense neuronal activity (Benjamin, 1982). Provocative data by Tsacopoulos (1995) suggest that ammonia released during neuronal activation serves as a signal to stimulate glial glycolysis (via activation of phosphofructokinase) (Lowry and Passonneau, 1966).…”

“…The non-ionized form is a readily diffusible molecule (Roos and Boron, 1981) that crosses the blood-brain barrier easily (Benjamin, 1982), whereas the ionized form does not readily pass cell membranes and can do so only by means of specific transporters (Flessner et al, 1992;Lande et al, 1994). Since the pKa of ammonia is 9.0, 98.3% of ammonia exists at physiologic pH (7.4) as the dissociated NH 4 ϩ ion.…”

“…The mechanism for the increase in glutamate in the extracellular space is not clear. Ammonia may depolarize neurons (Benjamin, 1982), resulting in excessive glutamate release. In rats with portacaval shunts (model of chronic HE), increased Ca 2ϩ -dependent (neuronal) glutamate release has been shown in situ using the cortical cup technique (Moroni et al, 1983), by in vivo microdialysis (Tossman et al 1987), and in hippocampal slices .…”

“…It is highly toxic to the CNS resulting in either seizures or coma (Benjamin, 1982; minase) (Cooper and Plum, 1987;Norenberg, 1981), defect in amino acid transport across the blood-brain barrier (James et al, 1978;Mans et al, 1982Mans et al, , 1983, and vasoparalysis (Kindt et al, 1977). It is not clear whether these changes are direct effects of ammonia or indirect effects of ammonia metabolism.…”