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Endocrine effects of 5-methoxytryptoline, 5-hydroxytryptoline and tryptoline, putative modulators of rat serotonergic system

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Abstract

The effects of tryptolines (THβCs), putative endogenous compounds acting on the serotonergic function, have been studied on endocrine parameters in rats. In particular, graded doses of 5-methoxytryptoline (5-MeOT), 5-hydroxytryptoline (5-OHT) and tryptoline (Tp) were ip or iv administered to the animals and the circulating titers of prolactin (PRL), growth hormone (GH) and luteinizing hormone (LH) were assayed either at 20 min or at various times after the injection of the compounds. The data herein reported show that THβCs exert endocrine effects, at least in a pharmacological condition. However, the three compounds unequally affect anterior pituitary function. In fact, while 5-MeOT, 5-OHT and Tp all enhance plasma PRL concentrations in a quick, short lasting and dose-related manner, 5-MeOT and Tp induce also decreases of serum LH levels in ovariectomized rats, and 5-MeOT only is able to diminish plasma GH titers. These findings underline an endocrine effect for THβCs in pharmacological conditions and may suggest a functional role for these compounds in the control of anterior pituitary function.

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References

  1. Barchas J.D., Elliott G.R., DoAmaral J.R., Erdelyi E., O’Connor S., Bowden M., Brodie H.K.H., Berger P.A., Renson J., Wyatt R.J. Tryptolines, formation from tryptamines and 5-MTHF by human platelets. Arch. Gen. Psychiatry 31: 862, 1974.

    Article  PubMed  CAS  Google Scholar 

  2. Hsu L.L, Mandell A.J. Enzymatic formation of tetrahydro-β-carboline from tryptamine and 5-methyltetrahydrofolic acid in rat brain fractions: regional and subcellular distribution. J. Neurochem. 24: 631, 1975.

    Article  PubMed  CAS  Google Scholar 

  3. Mandel L.R., Rosegay A., Walker R.W., Vanden Heuvel W.J.A. 5-methyltetrahydrofolic acid as a mediator in the formation of pyridoindoles. Science 186: 741, 1974.

    Article  PubMed  CAS  Google Scholar 

  4. Meller E., Rosengarten H., Friedhoff A.J. Conversion of 14C-S-adenosylmethionine to 14-formaldehyde and condensation with indoleamines: a side reaction in N-methyltransferase assay in blood. Life Sci. 14: 2167, 1974.

    Article  PubMed  CAS  Google Scholar 

  5. Rommelspacher H., Coper H., Strauss S. On the mode of formation of tetrahydro-β-carbolines. Life Sci. 18: 81, 1976.

    Article  PubMed  CAS  Google Scholar 

  6. Rosengarten H., Meiler E., Friedhoff A.J. Synthesis of tetrahydro-β-carbolines from indoleamines via enzymatic formation of formaldehyde from 5-methyltetrahydrofolic acid. Biochem. Pharmacol. 24: 1759, 1975.

    Article  PubMed  CAS  Google Scholar 

  7. Buckholtz N.S. Neurobiology of tetrahydro-β-carbolines. Life Sci. 27: 893, 1980.

    Article  PubMed  CAS  Google Scholar 

  8. Barker S.A., Harrison R.E.W., Brown G.B., Christian S.T. Gas chromatographic/mass spectrometric evidence for the identification of 1,2,3,4-tetrahydro-β-carboline as in vivo constituent of rat brain. Biochem. Biophys. Res. Commun 87: 146, 1979.

    Article  PubMed  CAS  Google Scholar 

  9. Barker S.A., Harrison R.E.W., Monte J.A., Brown G.B., Christian S.T. Identification and quantification of 1,2,3,4-tetrahydro-β-carboline, 2-methyl-1,2,3,4-tetrahydro-β-carboline and 6-methoxy-1,2,3,4-tetrahydro-β-carboline as in vivo constituents of rat brain and adrenal gland. Biochem. Pharmacol. 30: 9, 1981.

    Article  PubMed  CAS  Google Scholar 

  10. Honecker H., Coper H. Tetrahydronorharmane (THN) and 6-hydroxynorharmane. Physiological components in platelets und urine of man. Naunyn Schmiedebergs Arch. Pharmacol. 302: R63, 1978.

    Article  Google Scholar 

  11. Honecker H., Rommelspacher H. Tetrahydronorharmane (tetrahydro-β-carboline), a physiological occuyring compound of indole-metabolism. Naunyn Schmiedebergs Arch. Pharmacol. 305: 135, 1978.

    Article  PubMed  CAS  Google Scholar 

  12. Kari I. 6-methoxy-1,2,3,4-tetrahydro-β-carboline in pineal gland of chicken and cock. FEBS Lett. 112: 277, 1981.

    Google Scholar 

  13. Langer S.Z., Lee C.R., Segonzac A.W., Tateishi T., Esnaud H., Schoemaker H., Wimblad B. Possible endocrine role of the pineal gland for 6-methoxytetrahydro-β-carboline, a putative endogenous neuromodulator of the 3H-imipramine recognition site. Eur. J. Pharmacol. 102: 379, 1984.

    Article  PubMed  CAS  Google Scholar 

  14. Leino M., Aho I.M., Kari E., Gynther I., Markkanen S. Effects of melatonin and 6-metoxy-tetrahydro-β-carboline in light induced retinal damage: a computerized morphometric method. Life Sci. 35: 1997, 1984.

    Article  PubMed  CAS  Google Scholar 

  15. Buckholtz N.S., Boggan W.O. Effect of tetrahydro-β-carbolines on MAO and serotonin uptake in mouse brain. Biochem. Pharmacol. 25: 2319, 1976.

    Article  PubMed  CAS  Google Scholar 

  16. Buckholtz N.S., Boggan W.O. Monoamine oxidase inhibition in brain and liver produced by β-carbolines: structure-activity relationship and substrate specificity. Biochem. Pharmacol. 26: 1991, 1977.

    Article  PubMed  CAS  Google Scholar 

  17. Meller E., Friedman E., Schweitzer J.W., Friedhoff A.J. Tetrahydro-β-carbolines: specific inhibitors of type A monoamine oxidase in rat brain. J. Neurochem. 28: 995, 1977.

    Article  PubMed  CAS  Google Scholar 

  18. Langer S.Z., Raisman R., Tahraoui L., Scatton B., Niddam R., Lee C.R., Claustre Y. Substituted tetrahydro-β-carbolines are possible candidates as endogenous ligand of the 3H-imipramine recognition site. Eur J. Pharmacol. 98: 153, 1984.

    Article  PubMed  CAS  Google Scholar 

  19. Rommelspacher H., Strauss S., Heyck Cohnitz C. Inhibition of 5-hydroxytryptamine uptake by tetrahydronorharmane in vivo. Naunyn Schmiedebergs Arch. Pharmacol. 303: 229, 1978.

    PubMed  CAS  Google Scholar 

  20. Airaksinen M.M., Ho B.T., An R., Taylor D. Major pharmacological effects of 6-methoxytetrahydro-β-carboline, a drug elevating the tissue 5-hydroxytryptamine level. Arzneim. Forsch. Drug. Res. 28: 42, 1978.

    CAS  Google Scholar 

  21. Meyer J.S., Buckholtz M.S., Boggan W.O. Serotonergic stimulation of pituitary-adrenal activity in the mouse. Neuroendocrinology 26: 312, 1978.

    Article  PubMed  CAS  Google Scholar 

  22. Buckholtz N.S., Ondo J.G. Tetrahydro-β-carbolines elevate plasma prolactin in male rats. Endocr. Res Commun. 7: 221, 1980.

    Article  PubMed  CAS  Google Scholar 

  23. Fang V.S., Ho B.T., Meitzer H.Y. Effect of 6-methoxy-tetrahydro-β-carboline on serum prolactin levels of male rats. Comm. Psychopharmacol. 2: 59, 1978.

    CAS  Google Scholar 

  24. Smythe G.A., Duncan M.W., Bradshaw J.E., Nicholson M.W. Effects of 6-methoxy-1,2,3,4-tetrahydro-β-carboline and yohimbine on hypothalamic monoamine status and pituitary hormone release in the rat. Aust. J. Biol. Sci. 36: 379, 1983.

    PubMed  CAS  Google Scholar 

  25. Airaksinen M.M., Sainio E.L., Leppaluoto J., Kari I. 6-methoxy-tetrahydro-β-carboline (pinoline): effect on plasma renin activity and aldosterone, TSH, LH and β-endorphin levels in rats. Acta Endocrinol. (Kbh.) 197: 525, 1984.

    Google Scholar 

  26. Ellis G.B., Desjardins C. Male rats secrete luteinizing hormone and testosterone episodically. Endocrinology 110: 1618, 1982.

    Article  PubMed  CAS  Google Scholar 

  27. Rovescalli A.C., Brunello N., Franzetti C., Racagni G. Interaction of putative endogenous tryptolines with the hypothalamic serotonergic system and prolactin secretion in adult male rats. Neuroendocrinology 43: 603, 1986.

    Article  PubMed  CAS  Google Scholar 

  28. Carlsson M., Svensson K., Carlsson O. Rat brain serotonin: biochemical and functional evidence for a sex difference. J. Neural Transmission 63: 297, 1985.

    Article  CAS  Google Scholar 

  29. Kalra S.P., Kalra P.S. Neural regulation of luteinizing hormone secretion in the rat. Endocr. Rev. 4: 311, 1983.

    Article  PubMed  CAS  Google Scholar 

  30. Becù de Villalobos D., Libertum C. Serotonin and male neuroendocrine function. In: Paulson J.D., Negro-Vilar A., Lucena E., Martini L. (Eds.), Andrology-male fertility and sterility. Academic Press, Orlando, Florida, 1986, p. 59.

    Google Scholar 

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Authors and Affiliations

  1. Center of Neuropharmacology, Institute of Pharmacology and Pharmacognosy, University of Milan, Via Balzaretti 9, 20133, Milano, Italy

    A. C. Rovescalli & N. Brunello

  2. Istituto di Farmacologia, University of Pavia, Viale Taramelli 14, 27100, Pavia, Italy

    Giorgio Racagni

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  1. A. C. Rovescalli
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  2. N. Brunello
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  3. Giorgio Racagni
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Rovescalli, A.C., Brunello, N. & Racagni, G. Endocrine effects of 5-methoxytryptoline, 5-hydroxytryptoline and tryptoline, putative modulators of rat serotonergic system. J Endocrinol Invest 10, 65–72 (1987). https://doi.org/10.1007/BF03347157

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  • DOI: https://doi.org/10.1007/BF03347157

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