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Inhibition of presynaptic catecholamine synthesis with alpha-methyl-para-tyrosine attenuates nocturnal melatonin secretion in humans.

Abstract

The catecholamine dopamine (D) is involved in the regulation of LH and PRL secretion, whereas a dysregulated noradrenergic system may contribute significantly to symptoms encountered in affective disorders. This explains the attraction of using alpha-methyl-para-tyrosine (AMPT) in neuroendocrine and psychiatric research, as it inhibits both neurotransmitters. PRL has been used as a marker of the effectiveness of AMPT in blocking D function, but no good marker for the effectiveness of AMPT in blocking norepinephrine (NE) is available. The purpose of this study was to determine whether melatonin (M) might serve as such a marker, as its production and secretion are regulated by NE. Seven subjects were given either AMPT or promethazine, which does not alter M secretion, in a randomized, double blind fashion, and 24-h M secretion was studied. Two-way analysis of variance revealed a significant difference in M secretion (F = 13.2; df = 17,102; P = 0.0013), with the following time points being different: 22, 23, 24, 1, 2, 3, 4, 5, and 6 h. Also, 24-h urinary 6-sulfatoxymelatonin excretion correlated highly with 24-h M secretion, expressed as the area under the curve in the AMPT experiment (r = 0.93; P = 0.002), which indicates that AMPT does not alter the metabolism of M. These results demonstrate for the first time that AMPT significantly attenuates nocturnal M secretion. It is concluded that M is a good marker for characterizing the effectiveness of AMPT in inhibiting sympathetic NE activity.

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  • Authors+Show Affiliations

    ,

    Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota 55905.

    , , , ,

    Source

    MeSH

    Adult
    Biomarkers
    Catecholamines
    Circadian Rhythm
    Double-Blind Method
    Female
    Humans
    Male
    Melatonin
    Methyltyrosines
    Norepinephrine
    Presynaptic Terminals
    Time Factors
    alpha-Methyltyrosine

    Pub Type(s)

    Clinical Trial
    Journal Article
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    7962283

    Citation

    Zimmermann, R C., et al. "Inhibition of Presynaptic Catecholamine Synthesis With Alpha-methyl-para-tyrosine Attenuates Nocturnal Melatonin Secretion in Humans." The Journal of Clinical Endocrinology and Metabolism, vol. 79, no. 4, 1994, pp. 1110-4.
    Zimmermann RC, Krahn L, Klee G, et al. Inhibition of presynaptic catecholamine synthesis with alpha-methyl-para-tyrosine attenuates nocturnal melatonin secretion in humans. J Clin Endocrinol Metab. 1994;79(4):1110-4.
    Zimmermann, R. C., Krahn, L., Klee, G., Delgado, P., Ory, S. J., & Lin, S. C. (1994). Inhibition of presynaptic catecholamine synthesis with alpha-methyl-para-tyrosine attenuates nocturnal melatonin secretion in humans. The Journal of Clinical Endocrinology and Metabolism, 79(4), pp. 1110-4.
    Zimmermann RC, et al. Inhibition of Presynaptic Catecholamine Synthesis With Alpha-methyl-para-tyrosine Attenuates Nocturnal Melatonin Secretion in Humans. J Clin Endocrinol Metab. 1994;79(4):1110-4. PubMed PMID: 7962283.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Inhibition of presynaptic catecholamine synthesis with alpha-methyl-para-tyrosine attenuates nocturnal melatonin secretion in humans. AU - Zimmermann,R C, AU - Krahn,L, AU - Klee,G, AU - Delgado,P, AU - Ory,S J, AU - Lin,S C, PY - 1994/10/1/pubmed PY - 1994/10/1/medline PY - 1994/10/1/entrez SP - 1110 EP - 4 JF - The Journal of clinical endocrinology and metabolism JO - J. Clin. Endocrinol. Metab. VL - 79 IS - 4 N2 - The catecholamine dopamine (D) is involved in the regulation of LH and PRL secretion, whereas a dysregulated noradrenergic system may contribute significantly to symptoms encountered in affective disorders. This explains the attraction of using alpha-methyl-para-tyrosine (AMPT) in neuroendocrine and psychiatric research, as it inhibits both neurotransmitters. PRL has been used as a marker of the effectiveness of AMPT in blocking D function, but no good marker for the effectiveness of AMPT in blocking norepinephrine (NE) is available. The purpose of this study was to determine whether melatonin (M) might serve as such a marker, as its production and secretion are regulated by NE. Seven subjects were given either AMPT or promethazine, which does not alter M secretion, in a randomized, double blind fashion, and 24-h M secretion was studied. Two-way analysis of variance revealed a significant difference in M secretion (F = 13.2; df = 17,102; P = 0.0013), with the following time points being different: 22, 23, 24, 1, 2, 3, 4, 5, and 6 h. Also, 24-h urinary 6-sulfatoxymelatonin excretion correlated highly with 24-h M secretion, expressed as the area under the curve in the AMPT experiment (r = 0.93; P = 0.002), which indicates that AMPT does not alter the metabolism of M. These results demonstrate for the first time that AMPT significantly attenuates nocturnal M secretion. It is concluded that M is a good marker for characterizing the effectiveness of AMPT in inhibiting sympathetic NE activity. SN - 0021-972X UR - https://www.unboundmedicine.com/medline/citation/7962283/Inhibition_of_presynaptic_catecholamine_synthesis_with_alpha_methyl_para_tyrosine_attenuates_nocturnal_melatonin_secretion_in_humans_ L2 - https://academic.oup.com/jcem/article-lookup/doi/10.1210/jcem.79.4.7962283 DB - PRIME DP - Unbound Medicine ER -