Interactions of Peptides and Monoamines in Central Neurons: Role of Second Messengers

  • George R. Siggins
  • André Ferron
  • Jorge Mancillas
  • Samuel Madamba
  • Floyd E. Bloom
Part of the Wenner-Gren Center International Symposium Series book series (WGCISS)


Our interest in receptor-receptor interactions and the involvement of second messengers started in the late 1960s, with the observation that noradrenaline (NA) and cyclic AMP augment the amplitude of excitatory postsynaptic potentials, while at the same time directly hyperpolarizing cerebellar Purkinje cells (Siggins et al., 1971; Hoffer et al., 1973). This finding was later extended by the studies of Foote et al. (see 1983) and Woodward et al. (1979), showing that NA, although directly inhibitory, also could enhance both inhibitory and excitatory responses to other transmitters. This augmentation of transmitter responses was termed “neuromodulation” by some but “enabling” by Bloom (1979). Because neuromodulation implies lack of a direct effect by the “neuromodulator”, whereas NA clearly has a direct inhibitory effect on most central neurons, we prefer to use the “enabling” term (see Siggins and Gruol, 1986).


Pyramidal Neuron Pyramidal Cell Vasoactive Intestinal Polypeptide Cerebellar Purkinje Cell Pyramidal Cell Layer 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bloom, F.E. (1979). Chemical integrative processes in the central nervous system. In Neurosciences–Fourth Intensive Study Program. (eds. Schmitt, F.O. and Worden, F.G. ). MIT Press, Cambridge, pp. 51–58.Google Scholar
  2. Delfs, J.R. and Dichter, M.A. (1983). Effects of somatostatin on mammalian cortical neurons in culture: physiological actions and unusual dose-response characteristics. J. Neurosci. 3, 1176–1188.Google Scholar
  3. Dodd, J. and Kelly, J.S. (1978). Is sanatostatin an excitatory transmitter in the hippocampus? Nature 273, 674–675.CrossRefGoogle Scholar
  4. Ferron, A., Siggins, G.R. and Bloom, F.E. (1985). Vasoactive intestinal polypeptide acts synergistically with noradrenaline to depress spontaneous discharge rate in cerebral cortical neurons. Proc. Natl. Acad. Sci. U.S.A. 82, 8810–8812.CrossRefGoogle Scholar
  5. Foote, S.L., Bloom, F.E. and Aston-Jones, G. (1983). Nucleus locus ceruleus: new evidence of anatomical and physiological specificity. Physiol. Rev. 63, 844–914.Google Scholar
  6. Hoffer, B. J., Siggins, G. R., Oliver, A. P., and Bloan, F. E. (1973). Activation of the pathway from locus coeruleus to rat cerebellar Purkinje neurons: Pharmacological evidence of noradrenergic central inhibition. J. Pharmacol. Exp. Therap. 184, 553–569.Google Scholar
  7. Houser, C.R., Crawford, G.D., Salvaterra, P.M. and Vaughn, J.E. (1985). Immunocytochemical localization of choline acetyltransferase in rat cerebral cortex: A study of cholinergic neurons and synapses. J. Comp. Neurol. 234, 17–34.CrossRefGoogle Scholar
  8. Malenka, R.C., Madison, D.V., Andrade, R. and Nicoll, R.A. (1986). Phorbol esters mimic some cholinergic actions in hippocampal pyramidal neurons. J. Neurosci. 6 (2), 475–480.Google Scholar
  9. Mancillas, J.R., Siggins, G.R. and Bloom, F.E. (1986). Somatostatin selectively enhances acetylcholine-induced excitations in rat hippocampnis and cortex. Proc. Natl. Acad. Sci. U.S.A., in press, 1986.Google Scholar
  10. Morrison, J.H., Benoit, R., Magistretti, P.J. and Bloom, F.E. (1983). Immunohistochemical distribution of pro-sanatostatin-related peptides in cerebral cortex. Brain Res. 262: 344–351.CrossRefGoogle Scholar
  11. Morrison, J.H., Benoit, R., Magistretti, P.J., Ling, N. and Bloom, F.E. (1982). Immunohistochemical distribution of prosanatostatin-related peptides in hippocampus. Neurosci. Lett. 34 137–142.CrossRefGoogle Scholar
  12. Olpe, H-R., Balcar, V.J., Bittiger, H., Rink, H. and Sieber, P. (1980). Central actions of sanatostatin. Eur. J. Pharmacol. 63 127–133.CrossRefGoogle Scholar
  13. Pittman, Q.J. and Siggins, G.R. (1981). Somatostatin hyperpolarizes hippocampal pyramidal cells in vitro. Brain Res. 221, 402–408.CrossRefGoogle Scholar
  14. Reisine, T. and Guild, S. (1985). Pertussis toxin blocks somatostatin inhibition of calcium mobilization and reduces the affinity of somatostatin receptors for agonists. J Pharm. Exper. Therap. 235, 551.Google Scholar
  15. Renaud, L.P., Pittman, Q.J., Blume, H.W., Lamour, Y. and Arnauld, E. In Central Nervous System Effects of Hypothalamic Hormones and Other Peptides (eds. Collu, et al.). Raven Press, New York pp. 147–161.Google Scholar
  16. Siggins, G. R., Oliver, A. P., Hoffer, B. J., and Bloom, F. E. (1971). Cyclic adenosine monophosphate and norepinephrine: Effects of transmembrane properties of cerebellar Purkinje cells. Science 171, 192–194.CrossRefGoogle Scholar
  17. Siggins, G.R. and Gruol, D.L. (1986). Mechanisms of transmitter action in the vertebrate central nervous system. In Handbook of Physiology, Volume on Intrinsic Regulatory Systems of the Brain. (ed. F.E. Bloom ). The American Physiological Society, Bethesda, Maryland, pp. 1–114.Google Scholar
  18. Somogyi, P., Hodgson, A.J., Smith, A.D., Nunzi, M.G., Gorio, A. and Wu, J-Y. (1984). Different populations of GABAergic neurons in the visual cortex and hippocampus of cat contain somatostatin or cholecystokinin-immunoreactive material. J. Neurosci. 4, 2590–2603.Google Scholar
  19. Stone, T.W. and Taylor, D.A. (1977). Microiontophoretic studies of the effects of cyclic nucleotides on excitability of neurones in the rat cerebral cortex. J. Physiol. 266, 523–543.Google Scholar
  20. Woodward, D.J., Moises, H.C, Waterhouse, B.D., Hoffer, B.J. and Freedman, R. (1979). Modulatory actions of norepinephrine in the central nervous system. Federation Proc. 38, 2109–2116.Google Scholar

Copyright information

© The Wenner-Gren Center 1987

Authors and Affiliations

  • George R. Siggins
  • André Ferron
  • Jorge Mancillas
  • Samuel Madamba
  • Floyd E. Bloom

There are no affiliations available

Personalised recommendations