Effect of probenecid on 5-hydroxyindoleacetic acid in cisternal cerebrospinal fluid of rats with portacaval anastomosis
Marcelle Bergerona b c, Margaret S. Swainb c d e, Eduardo Molina‐Holgadob d, Tom�s A. Readerb d, Roger F. Butterworthc e
- aNeuroscience Research Unit, André-Viallet Clinical Research Centre, Hôpital Saint-Luc, Montréal, Québec, Canada
- bDepartment of Physiology, University of Montreal, Montreal, Canada
- cNeuroscience Research Unit, Hôpital Saint-Luc, Montréal, CANADA
- dDepartment of Physiology, University of Montreal, Montreal, Qué, Canada
- eNeuroscience Research Unit, Hôpital Saint-Luc, 1058 St-Denis St., H2X 3J4, Montréal, (Québec, CANADA
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Abstract
Portal-systemic encephalopathy (PSE) is characterized by a neuropsychiatric disorder progressing through personality changes, to stupor and coma. Previous studies have revealed alterations of serotonin and of its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in brain tissue and CSF in experimental (rat) and human PSE. Increased brain 5-HIAA concentrations could result from its decreased removal rather than to increased serotonin metabolism. In order to evaluate this possibility, CSF 5-HIAA concentrations were measured using an indwelling cisterna magna catheter technique at various times following end-to-side portacaval anastomosis in rats (the most widely used animal model of PSE) treated with probenecid, a competitive inhibitor that blocks the active transport of acid metabolites out of the brain and CSF. Following portacaval anastomosis and probenecid treatment, CSF concentrations of 5-HIAA were increased to a greater extent than in sham-operated controls. When data were expressed as per-cent baseline values, the relative increase of CSF 5-HIAA in portacaval shunted rats following probenecid treatment was not significantly different from sham-operated controls. These findings confirm that increased 5-HIAA in the CNS in experimental PSE results from increased 5HT metabolism or turnover and that the probenecidsensitive acid metabolite carrier is intact in PSE.
TL;DRIt is confirmed that increased 5-HIAA in the CNS in experimental PSE results from increased 5HT metabolism or turnover and that the probenecid-sensitive acid metabolite carrier is intact in PSE. (Semantic Scholar)