Effects of α-methyl-meta-tyrosine, α-methyl-meta-tyramine and metaraminol on the serotonin content in preparations of whole tissue and synaptosomes from the telencephalon of the pigeon

W. J. McBride, M. H. Aprison, J. N. Hingtgen

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Abstract

Whole tissue and preparations of synaptosomes from the telencephalon of the pigeon were used to study the effects of α-methyl-m-tyrosine (α-MMT), α-methyl-m-tyramine (α-MMTA) and metaraminol on the metabolism, uptake and release of serotonin (5-HT). Approximately 3·5 hr after an intramuscular injection of α-MMT (100 mg/kg), the levels of 5-HT decreased from 5·95 to 4·90 nmol/g tissue and the levels of 5-hydroxyindoleacetic acid (5-HIAA) decreased from 1·57 to 1·09 nmol/g tissue. Using an incubated crude synaptosomal preparation, it appeared that neither the uptake of [14C]-5-HT nor its conversion to 5-HIAA was inhibited by α-MMT. In addition, α-MMT did not seem to have an effect on the release of [14C]-5-HT from synaptosomes preloaded with radioactive 5-HT. However, two metabolites of α-MMT, namely, α-MMTA and metaraminol, significantly increased the release of (14C]-5-HT. Individually, at concentrations of 0·25 mg/ml, these two metabolites increased the efflux of [14C]-5-HT 14-17 fold from isolated synaptosomes. In combination and at lower concentrations of 0·025 and 0·005 mg/ml, there was a 6- and 2-fold increase, respectively, in efflux of [14C]-5-HT from isolated synaptosomes. α-MMTA and metaraminol also decreased the efflux of [14C]-5-HIAA; α-MMT did not appear to have any noticeable effect on the release of 5-HIAA. The results are discussed in terms of the behavioral effects produced by α-MMT in pigeons working on a multiple FR 50 FI 10 schedule of reinforcement.

Original languageEnglish
Pages (from-to)769-776
Number of pages8
JournalNeuropharmacology
Volume12
Issue number8
DOIs
StatePublished - 1973

Fingerprint

Metaraminol
Telencephalon
Synaptosomes
Columbidae
Serotonin
Hydroxyindoleacetic Acid
3-tyrosine
3-tyramine
Reinforcement Schedule
Intramuscular Injections
2-methylcyclopentadienyl manganese tricarbonyl

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

Cite this

Effects of α-methyl-meta-tyrosine, α-methyl-meta-tyramine and metaraminol on the serotonin content in preparations of whole tissue and synaptosomes from the telencephalon of the pigeon. / McBride, W. J.; Aprison, M. H.; Hingtgen, J. N.

In: Neuropharmacology, Vol. 12, No. 8, 1973, p. 769-776.

Research output: Contribution to journalArticle

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abstract = "Whole tissue and preparations of synaptosomes from the telencephalon of the pigeon were used to study the effects of α-methyl-m-tyrosine (α-MMT), α-methyl-m-tyramine (α-MMTA) and metaraminol on the metabolism, uptake and release of serotonin (5-HT). Approximately 3·5 hr after an intramuscular injection of α-MMT (100 mg/kg), the levels of 5-HT decreased from 5·95 to 4·90 nmol/g tissue and the levels of 5-hydroxyindoleacetic acid (5-HIAA) decreased from 1·57 to 1·09 nmol/g tissue. Using an incubated crude synaptosomal preparation, it appeared that neither the uptake of [14C]-5-HT nor its conversion to 5-HIAA was inhibited by α-MMT. In addition, α-MMT did not seem to have an effect on the release of [14C]-5-HT from synaptosomes preloaded with radioactive 5-HT. However, two metabolites of α-MMT, namely, α-MMTA and metaraminol, significantly increased the release of (14C]-5-HT. Individually, at concentrations of 0·25 mg/ml, these two metabolites increased the efflux of [14C]-5-HT 14-17 fold from isolated synaptosomes. In combination and at lower concentrations of 0·025 and 0·005 mg/ml, there was a 6- and 2-fold increase, respectively, in efflux of [14C]-5-HT from isolated synaptosomes. α-MMTA and metaraminol also decreased the efflux of [14C]-5-HIAA; α-MMT did not appear to have any noticeable effect on the release of 5-HIAA. The results are discussed in terms of the behavioral effects produced by α-MMT in pigeons working on a multiple FR 50 FI 10 schedule of reinforcement.",
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AB - Whole tissue and preparations of synaptosomes from the telencephalon of the pigeon were used to study the effects of α-methyl-m-tyrosine (α-MMT), α-methyl-m-tyramine (α-MMTA) and metaraminol on the metabolism, uptake and release of serotonin (5-HT). Approximately 3·5 hr after an intramuscular injection of α-MMT (100 mg/kg), the levels of 5-HT decreased from 5·95 to 4·90 nmol/g tissue and the levels of 5-hydroxyindoleacetic acid (5-HIAA) decreased from 1·57 to 1·09 nmol/g tissue. Using an incubated crude synaptosomal preparation, it appeared that neither the uptake of [14C]-5-HT nor its conversion to 5-HIAA was inhibited by α-MMT. In addition, α-MMT did not seem to have an effect on the release of [14C]-5-HT from synaptosomes preloaded with radioactive 5-HT. However, two metabolites of α-MMT, namely, α-MMTA and metaraminol, significantly increased the release of (14C]-5-HT. Individually, at concentrations of 0·25 mg/ml, these two metabolites increased the efflux of [14C]-5-HT 14-17 fold from isolated synaptosomes. In combination and at lower concentrations of 0·025 and 0·005 mg/ml, there was a 6- and 2-fold increase, respectively, in efflux of [14C]-5-HT from isolated synaptosomes. α-MMTA and metaraminol also decreased the efflux of [14C]-5-HIAA; α-MMT did not appear to have any noticeable effect on the release of 5-HIAA. The results are discussed in terms of the behavioral effects produced by α-MMT in pigeons working on a multiple FR 50 FI 10 schedule of reinforcement.

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