Skip to main content
Log in

Noradrenaline synthesis and utilization: Control by nerve impulse flow under normal conditions and after treatment with alpha-adrenoreceptor blocking agents

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

Summary

The changes in the synthesis and utilization of noradrenaline cranial and caudal to an acute section of the rat spinal cord have been used to investigate the importance of nerve impulses for these processes.

  1. 1.

    Cranial to a lesion of the spinal cord, the α-methyltyrosine-induced disappearance of noradrenaline was accelerated by the α-adrenoreceptor blocking agents yohimbine (10 mg/kg), piperoxan (60 mg/kg) and tolazoline (50 mg/kg). In the absence of nerve impulses caudal to a lesion of the spinal cord, this disappearance was decelerated as compared to that cranial to the lesion and it was not influenced by the three α-adrenoreceptor blocking agents.

  2. 2.

    The nialamide-induced accumulation of normetanephrine in the whole brain was increased by phenoxybenzamine (20 mg/kg) and yohimbine whereas it was decreased by the α-adrenoreceptor stimulating agent clonidine (0.1 mg/kg). The effect of clonidine was completely antagonized by yohimbine, but not by phenoxybenzamine, giving further evidence for the view that clonidine and yohimbine have a stronger effect than phenoxybenzamine on the α-adrenoreceptors regulating the release of noradrenaline induced by nerve impulses.

  3. 3.

    The accumulation of Dopa after decarboxylase inhibition cranial to a lesion of the spinal cord was accelerated by yohimbine, piperoxan and tolazoline, but not significantly affected by phenoxybenzamine and haloperidol (10 mg/kg). In the absence of nerve impulses caudal to a lesion of the spinal cord, the Dopa accumulation was decelerated as compared to that cranial to the lesion and it was not influenced by the former three α-adrenoreceptor blocking agents as well as by clonidine.

  4. 4.

    The results show that the synthesis and the utilization of noradrenaline normally, as well as the accelerations of these processes by α-adrenoreceptor blocking agents, are dependent on nerve impulses. The stimulation of the synthesis and utilization of noradrenaline by nerve impulses might be influenced via the activity of the α-adrenoreceptors located either on the nerve terminals or on the cell bodies or on both parts of the noradrenergic neurones. In the absence of nerve impulses, a receptor-mediated feed-back mechanism similar to that described for the synthesis of dopamine does not appear to regulate the synthesis of noradrenaline.

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

  • Agid, Y., Javoy, F., Glowinski, J.: Chemical or electrolytic lesion of the substantia nigra: early effects on neostriatal dopamine metabolism. Brain Res. 74, 41–49 (1974)

    Google Scholar 

  • Andén, N.-E., Börjesson, B., Magnusson, T.: Normetanephrine accumulation in the spinal cord due to nerve impulse activity. Europ. J. Pharmacol. 4, 349–351 (1968)

    Google Scholar 

  • Andén, N.-E., Grabowska, M., Strömbom, U.: Different alpha-adrenoreceptors in the central nervous system mediating biochemical and functional effects of clonidine and receptor blocking agents. Naunyn-Schmiedeberg's Arch. Pharmacol. 292, 43–52 (1976)

    Google Scholar 

  • Andén, N.-E., Bédard, P., Fuxe, K., Ungerstedt, U.: Early and selective increase in brain dopamine levels after axotomy. Experientia (Basel) 28, 300–301 (1972)

    Google Scholar 

  • Andén, N.-E., Corrodi, H., Fuxe, K., Hökfelt, T.: Increased impulse flow in bulbospinal noradrenaline neurons produced by catecholamine receptor blocking agents. Europ. J. Pharmacol. 2, 59–64 (1967)

    Google Scholar 

  • Andén, N.-E., Corrodi, H., Fuxe, K., Ungerstedt, U.: Importance of nervous impulse flow for the neuroleptic induced increase in amine turnover in central dopamine neurons. Europ. J. Pharmacol. 15, 193–199 (1971)

    Google Scholar 

  • Andén, N.-E., Häggendal, J., Magnusson, T., Rosengren, E.: The time course of the disappearance of noradrenaline and 5-hydroxytryptamine in the spinal cord after transection. Acta physiol. scand. 62, 115–118 (1964)

    Google Scholar 

  • Andén, N.-E., Corrodi, H., Dahlström, A., Fuxe, K., Hökfelt, T.: Effects of tyrosine hydroxylase inhibition on the amine levels of central monoamine neurons. Life Sci. 5, 605–611 (1966)

    Google Scholar 

  • Andén, N.-E., Corrodi, H., Fuxe, K., Hökfelt, B., Hökfelt, T., Rydin, C., Svensson, T.: Evidence for a central noradrenaline receptor stimulation by clonidine. Life Sci. 9 (I), 513–523 (1970)

    Google Scholar 

  • Atack, C. V., Magnusson, T.: Individual elution of noradrenaline (together with adrenaline), dopamine, 5-hydroxytryptamine and histamine from a single, strong cation exchange column, by means of mineral acid-organic solvent mixtures. J. Pharm. Pharmacol. 22, 625–627 (1970)

    Google Scholar 

  • Axelrod, J.: Methylation reactions in the formation and metabolism of catecholamines and other biogenic amines. Pharmacol. Rev. 18, 95–113 (1966)

    Google Scholar 

  • Besson, M. J., Cheramy, A., Gauchy, C., Glowinski, J.: In vivo continuous estimation of 3H-dopamine synthesis and release in the cat caudate nucleus: effects of α-methyl-p-tyrosine and of transection of the nigro-neostriatal pathway. Naunyn-Schmiedeberg's Arch. Pharmacol. 278, 101–105 (1973)

    Google Scholar 

  • Carlsson, A.: Discussion. In: Adrenergic mechanisms, J. R. Vane, G. E. W. Wolstenholme and M. O'Connor, eds., pp. 558–559. London: Churchill 1960

    Google Scholar 

  • Carlsson, A., Lindqvist, M.: A method for the determination of normetanephrine in brain. Acta physiol. scand. 54, 83–86 (1962)

    Google Scholar 

  • Carlsson, A., Waldeck, B.: A method for the fluorimetric determination of 3-methoxytyramine in tissues and the occurrence of this amine in brain. Scand. J. clin. Lab. Invest. 16, 133–138 (1964)

    Google Scholar 

  • Carlsson, A., Falck, B., Fuxe, K., Hillarp, N.-Å.: Cellular localization of monoamines in the spinal cord. Acta physiol. scand. 60, 112–119 (1964)

    Google Scholar 

  • Carlsson, A., Davis, 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 

  • Corrodi, H., Hanson, L. C. F.: Central effects of an inhibitor of tyrosine hydroxylation. Psychopharmacologia (Berl.) 10, 116–125 (1966)

    Google Scholar 

  • Dahlström, A., Fuxe, K.: Evidence for the existence of monoamine neurons in the central nervous system. II. Experimentally induced changes in the intraneuronal amine levels of bulbo-spinal neuron systems. Acta physiol. scand. 64, Suppl. 247, 1–36 (1965)

    Google Scholar 

  • Häggendal, J.: An improved method for fluorimetric determination of small amounts of adrenaline and noradrenaline in plasma and tissues. Acta physiol. scand. 59, 242–254 (1963)

    Google Scholar 

  • Kehr, W.: Temporal changes in catecholamine synthesis of rat forebrain structures after axotomy. J. Neural Transmission 35, 307–317 (1974)

    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 (1972a)

    Google Scholar 

  • Kehr, W., Carlsson, A., Lindqvist, M., Magnusson, T., Atack, C.: Evidence for a receptor-mediated feedback control of striatal tyrosine hydroxylase activity. J. Pharm. Pharmacol. 24, 744–747 (1972b)

    Google Scholar 

  • Magnusson, T.: Effect of chronic transection on dopamine, noradrenaline and 5-hydroxytryptamine in the rat spinal cord. Naunyn-Schmiedeberg's Arch. Pharmacol. 278, 13–22 (1973)

    Google Scholar 

  • Spector, S., Sjoerdsma, A., Udenfriend, S.: Blockade of endogenous norepinephrine synthesis by α-methyltyrosine, an inhibitor of tyrosine hydroxylase. J. Pharmacol. exp. Ther. 147, 86–95 (1965)

    Google Scholar 

  • Stanton, E. S., Smolen, P. M., Nashold B. S., Jr., Dreyer, D. A., Davis, J. N.: Segmental analysis of spinal cord monoamines after thoracic transection in the dog. Brain Res. 89, 93–98 (1975)

    Google Scholar 

  • Stock, G., Magnusson, T., Andén, N.-E.: Increase in brain dopamine after axotomy or treatment with gammahydroxybutyric acid due to elimination of the nerve impulse flow. Naunyn-Schmiedeberg's Arch. Pharmacol. 278, 347–361 (1973)

    Google Scholar 

  • Walters, J. R., Roth, R. H.: Dopaminergic neurons: drug-induced antagonism of the increase in tyrosine hydroxylase activity produced by cessation of impulse flow. J. Pharmacol. exp. Ther. 191, 82–91 (1974)

    Google Scholar 

  • Walters, J. R., Roth, R. H., Aghajanian, G. K.: Dopaminergic neurons: similar biochemical and histochemical effects of γ-hydroxybutyrate and acute lesions of the nigro-neostriatal pathway. J. Pharmacol. exp. Ther. 186, 630–639 (1973)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Grabowska, M., Andén, NE. Noradrenaline synthesis and utilization: Control by nerve impulse flow under normal conditions and after treatment with alpha-adrenoreceptor blocking agents. Naunyn-Schmiedeberg's Arch. Pharmacol. 292, 53–58 (1976). https://doi.org/10.1007/BF00506489

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00506489

Key words

Navigation