Phenylketonuria (PKU) causes mental retardation in children. The underlying cause of PKU is not well understood. The critical biochemical parameters and reaction in the development of PKU is plasma phenylalanine elevation whereas tyrosine is maintained at a relatively low level. The serotonergic system has consistently been implicated in the pathogenesis of PKU. The goal of this research is to determine if changes in serotonin receptors (5-HT2C) contribute to the conditions associated with PKU by inducing the primary characteristics of PKU beginnings in 9-day-old rats. To achieve this goal, animal models of PKU will be used to examine a number of pharmacological parameters, including quantitation of serotonin levels by means of high performance liquid chromatography (HPLC), and radioligand binding assays that are coupled with determinations of blood phenylalanine levels. The findings of this work may contribute toward an understanding of the mechanisms involved in this disease.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
1R15HD037118-01A1
Application #
6024029
Study Section
Special Emphasis Panel (ZRG1-BDCN-5 (01))
Program Officer
Hanson, James W
Project Start
2000-08-08
Project End
2004-07-31
Budget Start
2000-08-08
Budget End
2004-07-31
Support Year
1
Fiscal Year
2000
Total Cost
$94,463
Indirect Cost
Name
Fisk University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
052144326
City
Nashville
State
TN
Country
United States
Zip Code
37208
Dale, Y; Mackey, V; Mushi, R et al. (2003) Simultaneous measurement of phenylalanine and tyrosine in phenylketonuric plasma and dried blood by high-performance liquid chromatography. J Chromatogr B Analyt Technol Biomed Life Sci 788:1-8