Skip to main content
Log in

Neurotensin and its amide analogue [Gln4]-neurotensin: effects on brain monoamine turnover

  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Summary

Intracerebroventricularly administered neurotensin and [Gln4]-neurotensin (50–200 μg) increased the formation of Dopa in different brain regions of rats after inhibition of the aromatic l-amino acid decarboxylase. For both neuropeptides these increases were dose dependent (20–150%). In the corpus striatum [Gln4]-neurotensin was twice as active as neurotensin and it tended to be more active also in other brain regions. The brain tyrosine concentrations were also increased. [Gln4]-neurotensin (100–200 μg) following inhibition of the aromatic l-amino acid decarboxylase, increased the accumulation of 5-hydroxytryptophan in all brain regions by 30–60%. In contrast, neurotensin was completely inactive. In both cases the brain tryptophan concentrations were increased. Both neurotensin and [Gln4]-neurotensin also accelerated the disappearance of dopamine, noradrenaline and 5-hydroxytryptamine after inhibition of monoamine synthesis. These results show an increased brain monoamine turnover induced by both neuropeptides.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Andén, N.-E., Fuxe, K., Hökfelt, T.: Effect of some drugs on central monoamine nerve terminals lacking nerve impulse flow. Eur. J. Pharmacol. 1, 226–232 (1967)

    Google Scholar 

  • Andén, N.-E., Corrodi, H., Fuxe, K.: Turnover studies using synthesis inhibition. In: Metabolism of amines in the brain (G. Hooper, ed.), pp. 38–47. London: McMillan 1969

    Google Scholar 

  • Atack, C. V.: The determination of dopamine by a modification of the dihydroxyindole fluorimetric assay. Br. J. Pharmacol. 48, 699–714 (1973)

    Google Scholar 

  • Atack, C., Lindqvist, M.: Conjoint native and orthophthaldialdehy-decondensate assays for the fluorimetric determination of 5-hydroxyindoles in brain. Naunyn-Schmiedeberg's Arch. Pharmacol. 279, 267–84 (1973)

    Google Scholar 

  • Atack, C., Magnusson, T.: A procedure for the isolation of noradrenaline (together with adrenaline), dopamine, 5-hydroxytryptamine and histamine from the same sample using a single column of strongly acidic cation exchange resin. Acta Pharmacol. Toxicol. (Kbh.) 42, 35–57 (1978)

    Google Scholar 

  • Bédard, P., Carlsson, A., Lindqvist, M.: Effect of a transverse cerebral hemisection on 5-hydroxytryptamine metabolism in the rat brain. Naunyn-Schmiedeberg's Arch. Pharmacol. 272, 1–15 (1972)

    Google Scholar 

  • Bertler, Å, Carlsson, A., Rosengren, E.: A method for the fluorimetric determination of adrenaline and noradrenaline in tissues. Acta Physiol. Scand. 44, 273–292 (1958)

    Google Scholar 

  • Bissette, G., Nemerolff, C. B., Loosen, P. T., Prange, A. J., Jr., Lipton, M. A.: Hypothermia and intolerance to cold induced by intracisternal administration of the hypothalamic peptide neurotensin. Nature (Lond.) 262, 607–609 (1976)

    Google Scholar 

  • Brown, M., Rivier, J., Vale, W.: Bombesin: potent effects on thermoregulation in the rat. Science 196, 998–1000 (1977)

    Google Scholar 

  • Carlsson, A., Lindqvist, M.: Effect of ethanol on the hydroxylation of tyrosine and tryptophan in rat brain in vivo. J. Pharm. Pharmacol. 25, 437–440 (1973)

    Google Scholar 

  • Carlsson, A., Lindqvist, M.: Dependence of 5-HT and catecholamine synthesis on precursor amino-acid levels in rat brain. Naunyn-Schmiedeberg's Arch. Pharmacol. 303, 157–164 (1978)

    Google Scholar 

  • Carlsson, A., Davies, J. N., Kehr, W., Lindqvist, M., Atack, C. V.: Simultaneous measurement of tyrosine and tryptophan hydroxylase activities in brain in vivo using an inhibitor of the aromatic amino acid decarboxylase. Naunyn-Schmiedeberg's Arch. Pharmacol. 275, 153–168 (1972)

    Google Scholar 

  • Carlsson, A., García-Sevilla, J. A., Magnusson, T.: Effects of peptides on brain monoamines and gross behaviour. In: Principles for central regulation of the endocrine system. Nobel Symposium 42. Stockholm June 8–10, 1978 (K. Fuxe, T. Hökfelt, and R. Luft, eds.). New York: Plenum Press (in press, 1979)

    Google Scholar 

  • Carraway, R., Leeman, S. E.: The isolation of a new hypotensive peptide, neurotensin, from bovine hypothalami. J. Biol. Chem. 248, 6854–6861 (1973)

    Google Scholar 

  • Carraway, R. E., Leeman, S. E.: The amino acid sequence of a hypothalamic peptide, neurotensin. J. Biol. Chem. 250, 1907–1911 (1975a)

    Google Scholar 

  • Carraway, R. E., Leeman, S. E.: The synthesis of neurotensin. J. Biol. Chem. 250, 1912–1918 (1975b)

    Google Scholar 

  • Clineschmidt, B. V., McGuffin, J. C.: Neurotensin administered intracisternally inhibits responsiveness of mice to noxius stimuli. Eur. J. Pharmacol. 46, 395–396 (1977)

    Google Scholar 

  • Folkers, K., Chang, D., Humphries, J., Carraway, R., Leeman, S. E., Bowers, C. Y.: Synthesis and activities of neurotensin, and its acid and amide analogs: Possible natural occurrence of [Gln4]-Neurotensin. Proc. Natl. Acad. Sci. U.S.A. 73, 3833–3837 (1976)

    Google Scholar 

  • García-Sevilla, J. A., Ahtee, L., Magnusson, T., Carlsson, A.: Opiate-receptor mediated changes in monoamine synthesis in rat brain. J. Pharm. Pharmacol. 30, 613–621 (1978)

    Google Scholar 

  • García-Sevilla, J. A., Magnusson, T., Carlsson, A.: Effect of intracerebroventricularly administered somatostatin on brain monoamine turnover. Brain Res. 155, 159–164 (1978)

    Google Scholar 

  • Hökfelt, T., Elde, R., Johansson, O., Ljungdahl, Å., Schultzberg, M., Fuxe, K., Goldstein, M., Nilsson, G., Pernow, B., Terenius, L., Ganten, D., Jeffwate, S. L., Renfeld, L., Said, S.: Distribution of peptide-containing neurons. In: Psychopharmacology: A generation of progress. (M. A. Lipton, A. DiMascio, and K. F. Killam, eds.), pp. 39–66. New York: Raven Press 1978

    Google Scholar 

  • Iversen, L. L., Iversen, S. D., Bloom, F., Douglas, C., Brown, M., Vale, W.: Calcium-dependent release of somatostatin and neurotensin from rat brain in vitro. Nature (Lond.) 273, 161–163 (1978)

    Google Scholar 

  • Kehr, W., Carlsson, A., Lindqvist, M.: A method for the determination of 3,4-dihydroxyphenylalanine (Dopa) in brain. Naunyn-Schmiedeberg's Arch. Pharmacol. 274, 273–280 (1972)

    Google Scholar 

  • Kehr, W., Lindqvist, M., Carlsson, A.: Distribution of dopamine in the rat cerebral cortex. J. Neural Transm. 38, 173–180 (1976)

    Google Scholar 

  • Kobayashi, R. M., Brown, M., Vale, W.: Regional distribution of neurotensin and somatostatin in rat brain. Brain Res. 126, 584–588 (1977)

    Google Scholar 

  • Lazarus, C. H., Brown, M. R., Perrin, M. H.: Distribution, localization and characteristics of neurotensin binding sites in the brain. Neuropharmacology 16, 625–629 (1977)

    Google Scholar 

  • Loosen, P. T., Nemeroff, C. B., Bissette, G., Burnett, G. B., Prange, A. J., Jr., Lipton, M. A.: Neurotensin-induced hypothermia in the rat: structure-activity studies. Neuropharmacology 17, 109–113 (1978)

    Google Scholar 

  • Magnusson, T., Carlsson, A., Fisher, G. H., Chang, D., Folkers, K.: Effect of synthetic Substance P on monoaminergic mechanisms in brain. J. Neural Transm. 38, 89–93 (1976)

    Google Scholar 

  • Nemeroff, C. B., Bissette, G., Prange, A. J., Jr., Loosen, P. T., Barlow, T. S., Lipton, M. A.: Neurotensin: central nervous system effects of a hypothalamic peptide. Brain Res. 128, 485–496 (1977)

    Google Scholar 

  • Uhl, G. R., Snyder, S. H.: Regional and subcellular distribution of brain neurotensin. Life Sci. 19, 1827–1832 (1976)

    Google Scholar 

  • Uhl, G. R., Snyder, S. H.: Neurotensin receptor binding, regional and subcellular distributions favor transmitter role. Eur. J. Pharmacol. 41, 89–91 (1977)

    Google Scholar 

  • Waalkes, T. P., Udenfriend, S.: A fluorimetric method for the estimation of tyrosine in plasma and tissues. J. Lab. Clin. Med. 50, 733–736 (1957)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

García-Sevilla, J.A., Magnusson, T., Carlsson, A. et al. Neurotensin and its amide analogue [Gln4]-neurotensin: effects on brain monoamine turnover. Naunyn-Schmiedeberg's Arch. Pharmacol. 305, 213–218 (1978). https://doi.org/10.1007/BF00498813

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00498813

Key words

Navigation