Inhibition of serum melatonin concentration and synthesis of brain indolealkylamines by monofluoromethyldopa in the rat.
The simultaneous effect of alpha-monofluoromethyldopa (MFMD) on the synthesis of rat brain indolealkylamines has been investigated both in the daytime and in the dark phase. The effect on serum melatonin concentration has also been determined in the dark period. MFMD inhibits 5-hydroxytryptophan decarboxylase in the pineal gland, hypothalamus, and the cerebral cortex. Simultaneous measurement of 5-hydroxytryptophan (5-HTP), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) levels in the three brain areas revealed that MFMD caused large increases in pineal 5-HTP concentrations and substantial decreases in pineal 5-HT and 5-HIAA both in the light and dark phases; a significant decrease in daytime hypothalamic 5-HT content after 7-h pretreatment; and a large increase in dark-phase cortical 5-HT concentration after 4-h pretreatment. Serum melatonin levels were also reduced by the action of MFMD in the dark period. The evidence suggests that differences occur in the rate-limiting steps in the indolealkylamine biosynthesis in the three brain areas.
A J
AJ
Bradbury
R E
RE
Giddins
J A
JA
Smith
D006916:5-Hydroxytryptophan / Q000032:analysis; D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000032:analysis; D007031:Hypothalamus / Q000378:metabolism; D007211:Indoles / Q000096:biosynthesis*; D008297:Male; D008550:Melatonin / Q000097:blood*; D008750:Methyldopa / Q000031:analogs & derivatives* / Q000494:pharmacology; D010870:Pineal Gland / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000032:analysis
D007211:Indoles; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D008750:Methyldopa; C019494:alpha-monofluoromethyldopa; D006916:5-Hydroxytryptophan; D001142:Aromatic-L-Amino-Acid Decarboxylases; D008550:Melatonin