Cerebrospinal fluid glutamine, tryptophan, and tryptophan metabolite concentrations in dogs with portosystemic shunts

David E. Holt Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104.

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Robert J. Washabau Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104.

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Sina Djali Department of Pediatrics and Pharmacology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.

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Betsy Dayrell-Hart Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Present address is SouthPaws Veterinary Referral Center, 6136 Brandon Ave, Springfield, VA 22150.

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Kenneth J. Drobatz Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104.

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Melvyn P. Heyes CuraGen Corporation, Branford, CT 06405.

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Michael B. Robinson Department of Pediatrics and Pharmacology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.

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Abstract

Objective—To determine whether glutamine (GLN), tryptophan (TRP), and tryptophan metabolite concentrations are higher in cerebralspinal fluid (CSF) dogs with naturally occurring portosystemic shunts (PSS), compared with control dogs.

Animals—11 dogs with confirmed PSS and 12 control dogs fed low- and high-protein diets.

Procedure—Cerebrospinal fluid and blood samples were collected from all dogs. Serum and CSF concentrations of GLN, alanine, serine, TRP, 5-hydroxyindoleacetic acid (5-HIAA), and quinolinic acid (QUIN) were measured.

Results—Cerebrospinal fluid concentrations of GLN, TRP, and 5-HIAA were significantly higher in PSS dogs, compared with control dogs fed high- or lowprotein diets. Cerebrospinal fluid QUIN concentration was significantly higher in PSS dogs, compared with control dogs fed the low-protein diet. Serum QUIN concentration was significantly lower in PSS dogs, compared with control dogs fed either high- or lowprotein diets.

Conclusions and Clinical Relevance—An increase in CNS GLN concentration is associated with high CSF concentrations of TRP and TRP metabolites in dogs with PSS. High CSF 5-HIAA concentrations indicate an increased flux of TRP through the CNS serotonin metabolic pathway, whereas high CSF QUIN concentrations indicate an increased metabolism of TRP through the indolamine-2,3-dioxygenase pathway. The high CSF QUIN concentrations in the face of low serum QUIN concentrations in dogs with PSS indicates that QUIN production from TRP is occurring in the CNS. High concentrations of QUIN and other TRP metabolites in the CNS may contribute to neurologic abnormalities found in dogs with PSS and hepatic encephalopathy. (Am J Vet Res 2002;63:1167–1171)

Abstract

Objective—To determine whether glutamine (GLN), tryptophan (TRP), and tryptophan metabolite concentrations are higher in cerebralspinal fluid (CSF) dogs with naturally occurring portosystemic shunts (PSS), compared with control dogs.

Animals—11 dogs with confirmed PSS and 12 control dogs fed low- and high-protein diets.

Procedure—Cerebrospinal fluid and blood samples were collected from all dogs. Serum and CSF concentrations of GLN, alanine, serine, TRP, 5-hydroxyindoleacetic acid (5-HIAA), and quinolinic acid (QUIN) were measured.

Results—Cerebrospinal fluid concentrations of GLN, TRP, and 5-HIAA were significantly higher in PSS dogs, compared with control dogs fed high- or lowprotein diets. Cerebrospinal fluid QUIN concentration was significantly higher in PSS dogs, compared with control dogs fed the low-protein diet. Serum QUIN concentration was significantly lower in PSS dogs, compared with control dogs fed either high- or lowprotein diets.

Conclusions and Clinical Relevance—An increase in CNS GLN concentration is associated with high CSF concentrations of TRP and TRP metabolites in dogs with PSS. High CSF 5-HIAA concentrations indicate an increased flux of TRP through the CNS serotonin metabolic pathway, whereas high CSF QUIN concentrations indicate an increased metabolism of TRP through the indolamine-2,3-dioxygenase pathway. The high CSF QUIN concentrations in the face of low serum QUIN concentrations in dogs with PSS indicates that QUIN production from TRP is occurring in the CNS. High concentrations of QUIN and other TRP metabolites in the CNS may contribute to neurologic abnormalities found in dogs with PSS and hepatic encephalopathy. (Am J Vet Res 2002;63:1167–1171)

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