THE CONVERSION OF [³H]TRYPTOPHAN TO 5‐[³H]HYDROXYTRYPTAMINE IN MOUSE BRAIN FOLLOWING DEPLETION OF PHENYLALANINE AND TYROSINE

Abstract— Phenylalanine ammmonia‐lyase (PAL), an enzyme which converts phenylalanine (Phe) and tyrosine (Tyr) to trans‐p‐cinnamic acid and trans‐p‐coumaric acid, respectively, was administered to mice and its effect on the conversion of [³H]tryptophan to 5‐[³H]HT in the brain was measured. Although PAL significantly depleted plasma Tyr, it has little or no effect on either brain Tyr or catecholamine concentrations. Endogenous brain tryptophan levels were significantly increased 2 h after PAL administration, brain 5‐HT was dramatically increased 4 h following PAL and each returned to baseline levels by 8 h. This return to baseline was accompanied by a marked decrease in the fraction of tryptophan converted to 5‐HT during a 20 min pulse period preceding death, suggesting the activation of a compensatory decrease in 5‐HT synthesis in response to increased 5‐HT concentration. These data suggest that PAL administration readily produces reversible alterations in 5‐HT synthesis and that this may be a fruitful approach to studying brain 5‐HT function.