Effects of p-chlorophenylalanine on the metabolism of serotonin from 5-hydroxytryptophan

W. J. McBride, P. E. Penn, T. P. Hyde, J. D. Lane, J. E. Smith

Research output: Contribution to journalArticle

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Abstract

The effects of D,L-ρ{variant}-chlorophenylalanine methyl ester (PCPA-methyl ester) and two of its metabolites, 2-(ρ{variant}-chlorophenyl)-ethylamine (PCPEA) and ρ{variant}-chlorophenylacetic acid (PCPAA), on the metabolism of serotonin (5-HT) from D,L-5-hydroxytryptophan (5-HTP) ware studied in vitro and in vivo using the telencephalon and brainstem of the rat. For in vivo studies and some in vitro experiments, rats were injected with either 100 mg/kg PCPA-methyl ester or saline alone on days 1, 2, and 3, and were killed on day 15. When the in vivo metabolism of 5-HT was to be studied, the saline group and the PCPA group of animals were injected with 75 μg/kg [3H]D,L-5-HTP 20 min before sacrificing. With respect to the values found for the saline-injected animals, the specific activity (S.A.; dpm/nmol) of 5-HIAA was significantly greater in the telencephanol and brainstem of the animals injected with PCPA-methyl ester. The S.A. of 5-HTP was the same in both groups; the S.A. of 5-HT was lower in the telencephalon of the PCPA group than in the saline group; in the brainstem, there was no difference. In both the saline- and PCPA-injected animals, the S.A. of 5-HIAA was greater than the S.A. of 5-HT. There was no difference between the saline- and PCPA-injected animals with regard to: (1)L-5-HTP decarboxylase activity; (2)L-5-HTP-induced release of [3H]5-HT in vitro from crude nerve ending fractions (P2); or (3) in vitro uptake of [3H]D,L-5-HTP and its conversion to [3H]5-HT using the P2 fraction. In vitro studies demonstrated that the PCPEA could directly cause a large increase in the release of [3H]5-HT from the P2 fraction, whereas PCPA and PCPAA had little or no apparent effect. The data were interpreted to suggest that in the telencephalon of the animals treated with PCPA-methyl ester, there was a higher turnover of 5-HT than was found in the saline-treated group.

Original languageEnglish
Pages (from-to)437-449
Number of pages13
JournalNeurochemical Research
Volume1
Issue number4
DOIs
StatePublished - Aug 1976

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Fenclonine
5-Hydroxytryptophan
Metabolism
Serotonin
Animals
Esters
Telencephalon
Brain Stem
Hydroxyindoleacetic Acid
Rats
Aromatic-L-Amino-Acid Decarboxylases
Acids
Nerve Endings
Metabolites
In Vitro Techniques

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry

Cite this

McBride, W. J., Penn, P. E., Hyde, T. P., Lane, J. D., & Smith, J. E. (1976). Effects of p-chlorophenylalanine on the metabolism of serotonin from 5-hydroxytryptophan. Neurochemical Research, 1(4), 437-449. https://doi.org/10.1007/BF00966235

Effects of p-chlorophenylalanine on the metabolism of serotonin from 5-hydroxytryptophan. / McBride, W. J.; Penn, P. E.; Hyde, T. P.; Lane, J. D.; Smith, J. E.

In: Neurochemical Research, Vol. 1, No. 4, 08.1976, p. 437-449.

Research output: Contribution to journalArticle

McBride, W. J. ; Penn, P. E. ; Hyde, T. P. ; Lane, J. D. ; Smith, J. E. / Effects of p-chlorophenylalanine on the metabolism of serotonin from 5-hydroxytryptophan. In: Neurochemical Research. 1976 ; Vol. 1, No. 4. pp. 437-449.
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