Age-related changes in tetrahydrobiopterin and GTP-cyclohydrolase activity in the brain and adrenal gland of rats.
In the present study, we observed that tetrahydrobiopterin (BH4) levels were decreased significantly in the striatum, substantia nigra, frontal cortex, hypothalamus, and cerebellum of 25-month-old and in the cerebellum only in case of 18-month-old rats as compared to 4-month-old rats. In contrast, BH4 levels in adrenal glands of 25-month-old rats were increased significantly. Kinetic analysis of GTP-cyclohydrolase revealed a decrease in the apparent Km along with an increase in Vmax value in the adrenal of 25-month-old rats compared to 4-month-old rats. Whereas, in cerebellum we observed that the apparent Km of the high affinity form of the enzyme was increased and a decrease in the Vmax value of the low affinity form only in case of 25-month-old rats compared to the young animals. These alterations in the BH4 levels and its synthesizing enzyme kinetics in specific brain areas and adrenal glands of aged rats are consistent with the reported changes in the catecholamine function in central and peripheral nervous system with aging.
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262, USA.
M A
MA
Hossain
J M
JM
Masserano
N
N
Weiner
D000311:Adrenal Glands / Q000201:enzymology*; D000375:Aging / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives* / Q000378:metabolism; D001921:Brain / Q000201:enzymology*; D002531:Cerebellum / Q000201:enzymology; D002851:Chromatography, High Pressure Liquid; D006136:GTP Cyclohydrolase / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
D001708:Biopterins; D006136:GTP Cyclohydrolase; C003402:sapropterin