TY - JOUR T1 - Brain and peripheral metabolism of 5-hydroxytryptophan-14C following peripheral decarboxylase inhibition. JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 545 LP - 555 VL - 197 IS - 3 AU - J J Warsh AU - H C Stancer Y1 - 1976/06/01 UR - http://jpet.aspetjournals.org/content/197/3/545.abstract N2 - Following selective peripheral decarboxylase inhibition, a greater fraction of peripherally measured monoamine metabolites should derive from central nervous system monoamine metabolism. In rats pretreated with the peripheral decarboxylase inhibitor L-alpha-(3,4-dihydroxybenzyl)-alpha-hydrazinopropionic acid (MK-486) (50 mg/kg i.p. or i.v.), the peripheral formation of 5-hydroxytryptamine-14C (5-HT-14C) from the precursor DL-5-hydroxytryptophan-14C (5-HTP-14C) was reduced by 82 to 100% over a 4-hour interval. There was a marked increase in the penetration of 5-HTP-14C into brain and in the appearance in brain of 5-HT-14C and 5-hydroxyindoleacetic acid-14C (5-HIAA-14C). The cerebral metabolism of 5-HTP-14C in vehicle-pretreated animals appeared to occur mainly in the brain vascular compartment. Following MK-486 pretreatment, the in vivo metabolism of 14C-5-hydroxyindoles in the extracerebral compartment obeys linear kinetics as does the uptake and decarboxylation of 5-HTP-14C in brains. The cerebral turnover of 5-HT-14C appeared to increase as a function of the dose of 5-HTP injected. This phenomenon may be a result of either saturation of brain 5-HT storage sites or nonspecific metabolism of 5-HTP in brain catecholamine neurons. A highly signigificant correlation was found between the brain and blood 5-HIAA-14C levels following MK-486. The adrenal formation of 5-HT, which was not inhibited by MK-486, did not appear to contribute significantly to the blood 5-HIAA-14c levels. These results suggest the possibility that following peripheral decarboxylase inhibition a larger fraction of peripherally measured 5-HIAA may derive from central nervous system 5-HT metabolism. ER -