Skip to main content

Cotransmitters: Pharmacological Implications

  • Conference paper
Basic Aspects of Receptor Biochemistry

Part of the book series: Journal of Neural Transmission ((NEURAL SUPPL,volume 18))

  • 42 Accesses

Summary

The discovery that two or more neuroactive substances coexist in the same nerve terminal suggests that two or more neuroactive compounds can be released by nerve impulses simultaneously and probably act cooperatively at postsynaptic sites. This interaction changes the models of synaptic transmission we have used in the past and imposes a reevaluation of current understanding of synaptic pharmacology. Neuroactive substances coexisting in the same axon terminal can function as “primary transmitter” if they activate the receptor-transducer system or as “cotransmitter” if they modulate the gain of the system. Two examples of synaptic mechanisms in which two neuroactive substances coexisting in the same axon terminal appear to function as primary transmitter and cotransmitter are discussed. These examples are: 1. the modulation of the function of nicotinic receptors of chromaffin cells by endogenous opiate peptides stored in the splanchnic nerve and 2. the modulation of GABA receptor function by benzodiazepines. The understanding of the mechanisms by which primary transmitter and cotransmitter interact at the postsynaptic site may be of obvious importance in elucidating the integrative and discriminative function of the nervous system, in interpreting the action of drugs and in developing new therapeutic agents devoid of untoward side effects.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 44.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Baraldi, M., Guidotti, A., Schwartz, J.P., Costa, E.: GABA receptors in clonal cell lines: A model for studying the benzodiazepine action at molecular level. Science 205, 821–825 (1979).

    Article  CAS  PubMed  Google Scholar 

  • Chan-Palay, V., Jonsson, V. G., Palay, S. L.: Serotonin and substance P coexist in neurones of the rat’s central nervous system. Proc. Natl. Acad. Sci. U.S.A. 75, 1582–1586 (1978).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Chan-Palay, V., Nilover, G., Palay, S. L., Beinfeld, M. C., Zimmerman, E. A., Wu,J. Y, O’Donohue, T. L.: Chemical heterogeneity in cerebellar Purkinje cells: Existence of glutamic acid decarboxylase-like and motilin-like immunoreactivities. Proc. Natl. Acad. Sci. U.S.A. 78, 7787–7791 (1981).

    CAS  Google Scholar 

  • Cheng, Y. C., Prusoff, W. H.: Relationship between the inhibition constant (Ki) and the concentration of inhibitor which causes 50 percent inhibition (IC50) of an enzymatic reaction. Biochem. Pharmacol. 22, 3099–3108 (1973).

    Article  CAS  PubMed  Google Scholar 

  • Costa, E.: Coexistence of putative neuromodulators in the same axon: Pharmacological consequences of receptors. In: Co-Transmission, New York: Raven Press. in press.

    Google Scholar 

  • Eccles, J. C., McGeer, P. L.: Ionotropic and metabotropic neurotransmission. Trends Neurosci. 2, 39–40 (1979).

    Article  Google Scholar 

  • Guidotti, A., Konkel, D. R., Ebstein, B., Corda, M. G., Wise, B. C., Krutzsch, H., Meek, J.L., Costa, E.: Isolation, characterization and purification to homogeneity of a rat brain protein (GABA-modulin). Proc. Natl. Acad. Sci. U.S.A. 79, 6084–6088 (1982).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Guidotti, A., Toffano, G., Costa, E.: An endogenous protein modulates the affinity of GABA and benzodiazepine receptors in rat brain. Nature 257, 553–555 (1978).

    Article  Google Scholar 

  • Hanbauer, I., Kelly, G.D., Saiani, L., Yang, H.-Y. T: Mets-enkephalin like peptides of the adrenal medulla: Release by nerve stimulation and functional implications. Peptides 3, 469–473 (1982).

    Article  CAS  PubMed  Google Scholar 

  • Hökfelt, T, Lundberg, J. M., Schultzberg, M., Johansson, O., Ljungdahl, A., Rehfeld,J.: Coexistence of peptides and putative transmitters in neurons. In: Neuronal Peptides and Neuronal Communication, p. 1. New York: Raven Press. 1980.

    Google Scholar 

  • Kumakura, K., Karoum, F., Guidotti, A., Costa, E.: Modulation of nicotinic receptors by opiate receptor agonists in cultured adrenal chromaffin cells. Nature 283, 489–492 (1980).

    Article  CAS  PubMed  Google Scholar 

  • Lemaire, S., Livett, B., Tseng, R., Mercier, P., Lemaire, I.: Studies on the inhibitory action of opiate compounds in isolated bovine chromaffin cells: Noninvolvement of stereospecific opiate binding sites. J. Neurochem. 36, 886–892 (1981).

    Article  CAS  PubMed  Google Scholar 

  • Massotti, M., Guidotti, A., Costa, E.: Characterization of benzodiazepine and y-aminobutyric acid recognition sites and their endogenous modulators. J. Neurosci. 1, 409–418 (1981).

    CAS  PubMed  Google Scholar 

  • Möhler, H., Wu, J. W., Richards, J. G.: Benzodiazepine receptors: Autoradio-graphical and immunochemical evidence for their localization in regions of GABAergic synaptic contacts. Adv. Biochem. Psychopharmacol. 26, 139–146 (1981).

    PubMed  Google Scholar 

  • Panula, P., Yang, H.-Y. T., Costa, E.: Coexistence of met5-enkephalin-Arg6Phe7 with mets-enkephalin and the possible role of met5-enkephalinArg6-Phe7 in neuronal function. In: Coexistence of Neuroactive Substances. New York: Raven Press. 1982 (in press).

    Google Scholar 

  • Saiani, L., Guidotti, A.: Opiate receptor mediated inhibition of catecholamine release in primary cultures of bovine adrenal chromaffin cells. J. Neurochem. 39, 1669–1676 (1982).

    Article  CAS  PubMed  Google Scholar 

  • Study, R. E., Barker, J. L.: Diazepam and (—)pentobarbital: Fluctuation analysis reveals different mechanisms for potentiation of y-aminobutyric acid responses in cultured central neurones. Proc. Natl. Acad. Sci. U.S.A. 78, 7180–7184 (1981).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Tallman, J.F., Thomas, J. W., Gallager, D. W: GABAergic modulation of benzodiazepine binding site sensitivity. Nature 274, 384–385 (1978).

    Article  Google Scholar 

  • Wise, B., Guidotti, A., Costa, E.: Phosphorylation induces a decrease in the biological activity of the protein inhibitor (GABA-modulin) of y-aminobutyric acid binding sites. Proc. Natl. Acad. Sci. U.S.A. 1982 (in press).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1983 Springer-Verlag Wien

About this paper

Cite this paper

Guidotti, A., Saiani, L., Wise, B.C., Costa, E. (1983). Cotransmitters: Pharmacological Implications. In: Goldstein, M., Jellinger, K., Riederer, P. (eds) Basic Aspects of Receptor Biochemistry. Journal of Neural Transmission, vol 18. Springer, Vienna. https://doi.org/10.1007/978-3-7091-4408-4_20

Download citation

  • DOI: https://doi.org/10.1007/978-3-7091-4408-4_20

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-7091-4410-7

  • Online ISBN: 978-3-7091-4408-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics