Ammonia and manganese increase arginine uptake in cultured astrocytes

Alan S. Hazell, Michael D. Norenberg

Research output: Contribution to journalArticle

40 Scopus citations


Recent work has suggested a possible role for nitric oxide (NO) in the development of hepatic encephalopathy (HE). In this study, we examined the effect of ammonia and manganese, factors implicated in the pathogenesis of HE, on the transport of arginine (a precursor of NO) into primary cultures of astrocytes. Treatment with 5 mM ammonia for 1-4 days produced a maximal (53%) increase in L-arginine uptake at 3 days when compared to untreated cells. Kinetic analysis following 4-day treatment with 5 mM ammonia revealed an 82% increase in the V(max) and a 61% increase in the K(m) value. Similar analysis with 100 μM manganese showed a 101% increase in V(max) and a 131% increase in the K(m) value. These results suggest that both manganese and ammonia alter L-arginine uptake by modifying the transporter for arginine. A decrease of 32% in the non-saturable component of L-arginine transport was also observed following treatment with ammonia. When cultures were treated separately with 5 mM ammonia and 100 μM manganese for 2 days, the uptake of L-arginine increased by 41% and 57%, respectively. Combined exposure led to no further increase in uptake. Our results suggest that ammonia and manganese may contribute to the pathogenesis of HE by influencing arginine transport and thus possibly NO synthesis in astrocytes.

Original languageEnglish (US)
Pages (from-to)869-873
Number of pages5
JournalNeurochemical Research
Issue number6
StatePublished - May 1 1998


  • Ammonia
  • Arginine transport
  • Astrocyte
  • Hepatic encephalopathy
  • Manganese

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry

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