Citrulline uptake in rat cerebral cortex slices: modulation by Thioacetamide -Induced hepatic failure.

Abstract

L-citrulline (Cit) is a co-product of NO synthesis and a direct L-arginine (Arg) precursor for de novo NO synthesis. Acute liver failure (ALF) is associated with increased nitric oxide (NO) and cyclic GMP (cGMP) synthesis in the brain, indirectly implicating a role for active transport of Cit. In the present study we characterized [(3)H]Cit uptake to the cortical brain slices obtained from control rats and rats with thioacetamide (TAA)-induced ALF ("TAA slices"). In both control and TAA slices the uptake was partially Na(+)-dependent and markedly inhibited by substrates of systems L and N, including L-glutamine (Gln), which accumulates in excess in brain during ALF. Cit uptake was not affected by Arg, the y(+)/y(+)L transport system substrate, nor by amino acids taken up by systems A, xc (-)or XAG. The Vmax of the uptake in TAA slices was ~60 % higher than in control slices. Chromatographic (HPLC) analysis revealed a ~30 % increase of Cit concentration in the cerebral cortical homogenates of TAA rats. The activity of argininosuccinate synthase (ASS) and argininosuccinate lyase (ASL), the two enzymes of Cit-NO cycle catalyzing synthesis of Arg, showed an increase in TAA rats, consistent with increased ASS and ASL protein expression, by ~30 and ~20 %, respectively. The increased Cit-NO cycle activity was paralleled by increased expression of mRNA coding for inducible nitric oxide synthase (iNOS). Taken together, the results suggest a role for Cit in the activation of cerebral NO synthesis during ALF.

• Authors: Magdalena Zielińska, Marta Obara-Michlewska, Wojciech Hilgier, Jan Albrecht
• Journal: Metabolic brain disease (Metab Brain Dis) Vol. 29 Issue 4 Pg. 1053-60 (Dec 2014) ISSN: 1573-7365 [Electronic] United States
• PMID: 24385142 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Nerve Tissue Proteins
• Thioacetamide
• Citrulline
• Nitric Oxide
• Arginine
• Argininosuccinate Lyase
• Argininosuccinate Synthase

Topics

• Animals
• Arginine (metabolism)
• Argininosuccinate Lyase (metabolism)
• Argininosuccinate Synthase (metabolism)
• Cerebral Cortex (metabolism)
• Citrulline (metabolism)
• In Vitro Techniques
• Kinetics
• Liver Failure (chemically induced, metabolism)
• Male
• Nerve Tissue Proteins (metabolism)
• Nitric Oxide (biosynthesis)
• Rats
• Rats, Sprague-Dawley
• Thioacetamide (toxicity)