PERIPHERAL AND CENTRAL SHORT-TERM EFFECTS OF FUSARIC ACID, A DBH INHIBITOR, ON TRYPTOPHAN AND SEROTONIN METABOLISM IN THE RAT
J. Neural Transmission. 1986-09-01; 65(3-4): 219-232
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1. J Neural Transm. 1986;65(3-4):219-32.
Peripheral and central short-term effects of fusaric acid, a DBH inhibitor, on
tryptophan and serotonin metabolism in the rat.
Chaouloff F, Laude D, Merino D, Serrurrier B, Elghozi JL.
Fusaric acid (FA) administration to the rats promoted one hour later a large
decrease in plasma total tryptophan (TRP), without affecting either plasma free
TRP or lipolysis, as measured by plasma non esterified fatty acid concentration.
The previous change was associated with hypoinsulinemia, hyperglycemia and
increased plasma corticosterone level. Regression analysis revealed a significant
correlation between brain TRP and the percentage of plasma TRP which was free
(i.e. unbound to albumin), both increased by FA injection. The increase in brain
TRP promoted an increased brain serotonin synthesis, as measured by the enhanced
brain and CSF 5-HIAA levels. Valine pretreatment, which blocks TRP entry into the
brain, completely prevented FA-induced brain TRP and brain 5-HIAA increases.
These results suggest that the increased brain serotonergic turnover following FA
treatment was due to a peripheral action of the drug upon TRP disposition. The
latter effect may be caused (i) by in vivo peripheral alterations in
catecholaminergic metabolism and (ii) by FA chemical structure since in vitro
experiments revealed that FA was able to displace TRP binding to albumin, thus
increasing the plasma free TRP pool.
PMID: 2423643 [Indexed for MEDLINE]