Receptor-Receptor Interactions in the Modulation of Nicotinic Receptors in Adrenal Medulla

  • E. Costa
  • I. Hanbauer
  • A. Guidotti


Many important studies directed to clarify the molecular nature of nicotinic receptor function were carried out using chromaffin cells of adrenal medulla as a model. Such a selection was motivated by the convenience of evaluating nicotinic receptor function through a simple measurement of the catecholamines that are released from either perfused adrenal gland or primary cultures of bovine chromaffin cells. For many years, the background rationale for all these studies included the tacit assumption that the release of catecholamines from chromaffin cells was exclusively regulated by acetylcholine (ACh) which was believed to be the only chemical signal released from splanchnic nerves that acts on nicotinic receptors of adrenal chromaffin cells. Moreover, it was believed that the exclusive function of chromaffin cells was the synthesis, storage and secretion of catecholamines. This simple model has been challenged by the discovery in adrenal chromaffin tissues and in their afferent neurons of a number of additional neuromodulators, including γ-aminobutyric acid (GABA) (Kataoka et al., 1984, Alho et al., 1985), substance P (Mizobe et al., 1979), enkephalins (Schultzberg et al., 1978, Yang et al., 1980) and NPY (Majane et al., 1985). The aim of the present paper is to reevaluate many of the literature’s tenets on nicotinic receptor function that resulted from an oversimplistic model of cholinergic transmission.


Chromaffin Cell Nicotinic Receptor Adrenal Medulla Opioid Peptide Splanchnic Nerve 
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  1. Allen, Y.S., Adrian, T.E., Allen, J.M., Tatemoto, K., Crow, T.J., Bloom, S.R. and Polak, J.M., 1983, Neuropeptide Y distribution in the rat brain, Science 221: 877–879.PubMedCrossRefGoogle Scholar
  2. Alho, H., Fujimoto, M., Guidotti, A., Hanbauer, I., Kataoka, Y. and Costa, E, 1985, Gamma aminobutyric acid (GABA) in the adrenal medulla: location, pharmacology and applications, in: Neurology and Neurobiology, ed., Pannula, Pavarinta, Soinila, Vol. 16, pp. 453–464, Alaskan, New York.Google Scholar
  3. Bormann, J. and Clapham, D.E., 1985, γ-aminobutyric acid receptor channels in adrenal chromaffin cells: A patch clamp study, Proc. Natl. Acad. Sci. 82: 2168–2172.Google Scholar
  4. Bowery, N.G., Price, G.W., Hudson, A.L., Hill, D.R., Wilkin, G.P. and Turnbull, M.J., 1984, GABA receptor multiplicity: visualization of different receptor types in the mammalian CNS, Neuropharmacology 23: 219–231.PubMedCrossRefGoogle Scholar
  5. Chavkin, C., Cox, B.M. and Goldstein, A., 1979, Stereospecific opiate binding in bovine adrenal medulla, Mol. Pharmacol. 15: 751–753.PubMedGoogle Scholar
  6. Clapham, D.E. and Neher, E., 1984, Substance P reduces acetylcholine- induced currents in isolated bovine chromaffin cells, J. Physiol. 347: 255–277.PubMedGoogle Scholar
  7. Costa, E., Corda, M.G. and Guidotti, A., 1983, On a brain polypeptide functioning as a putative effector for the recognition sites of benzodiazepine and beta-carboline derivatives, Neuropharmacology 27: 1481–1492.CrossRefGoogle Scholar
  8. Costa, E. and Guidotti, A., 1979, Molecular mechanisms in the receptor action of benzodiazepine, Ann. Rev. Pharmacol. Toxiol. 19: 531–545.CrossRefGoogle Scholar
  9. Govoni, S., Hanbauer, I., Hexum, T.D., Yang, H-Y.T., Kelly, G.D. and Costa E, 1981, In vivo characteristics of the mechanisms that secrete enkephalin like peptides stored in dog adrenal medulla, Neuropharmacology 20: 639–645.PubMedCrossRefGoogle Scholar
  10. Gray, T.S. and Morely, J.E., 1986, Neuropeptide Y: Anatomical distribution and possible function in mammalian nervous system, Life Sci. 38: 389–401.PubMedCrossRefGoogle Scholar
  11. Guidotti, A., Corda, M.G., Wise, B.C., Vaccarino, F. and Costa, E., 1983, GABAergic synapses, Neuropharmacology 22: 1471–1479.PubMedCrossRefGoogle Scholar
  12. Haring, Stahli, C., Schoch, B., Takacs, B., Staehelin, T. and Mohler, H., 1985, Monoclonal antibodies reveal structural homogeneity of γ-aminobutyric acid/benzodiazepine receptors in different brain areas, Proc. Natl. Acad. Sci. 82: 4837–4841.Google Scholar
  13. Hexum, T.D., Hanbauer, I., Govoni, S., Yang, H-Y.T., Kelly, G.D. and Costa, E., 1980, Secretion of enkephalin-like peptides from canine adrenal gland following splanchnic nerve stimulation, Neuropeptides 1: 137–142.CrossRefGoogle Scholar
  14. Higuchi, H., Costa, E. and Yang, H-Y.T., 1986, Inhibition of catecholamine release from bovine chromaffin cells by neuropeptide Y and specific binding of N-[pripionyl-3H] neuropeptide Y in bovine adrenal membrane, J. Pharmacol. Exp. Ther., in press.Google Scholar
  15. Higuchi, H., Yang, H-Y.T. and Costa, E., 1986, Age-related change in neuropeptide Y-like immunoreactive peptides in rat adrenal glands, brains and blood, MoI. Pharmacol. 1986, in press.Google Scholar
  16. Hilton, J.G., Weaver, D.C., Muelheims, C., Glaviano, V.V. and Wegria, R., 1958, Perfusion of the isolated adrenals in situ, Am. J. Physiol. 192: 525–530.Google Scholar
  17. Kataoka, Y., Gutman, Y., Guidotti, A., Pannula, P., Wroblewski, J., Cosenza-Murphy, D., W.V. J.Y. and Costa, E., 1984, Intrinsic GABAergic system of adrenal chromaffin cells, Proc. Natl. Acad. Sci. 81: 3218–3222.Google Scholar
  18. Kataoka, Y., Fujimoto, M., Alho, H., Guidotti, A., Geffard, M., Kelly, G.D. and Hanbauer, I., 1986, Intrinsic GABA receptors modulate the release of catecholamines from canine adrenal gland in situ, J. Pharmacol. Exp. Ther., in press.Google Scholar
  19. Kumakura, K., Karoum, F., Guidotti, A. and Costa, E., 1980, Modulation of nicotinic receptors by opiate receptor agonists in cultured adrenal chromaffin cells, Nature 283: 489–492.PubMedCrossRefGoogle Scholar
  20. Majane, E.A., Alho, H., Kataoka, K., Lee, C.H. and Yang, H-Y.T., 1985, Neuropeptide Y in bovine glands: distribution and characterization, Endocrinology 117: 1162–1168.PubMedCrossRefGoogle Scholar
  21. Mizobe, F., Kozousek, V., Dean, D.M. and Livett, B.G., 1979, Pharmacological characterization of adrenal paraneurons: Substance P and somatostatin as inhibitory modulators of the nicotinic response, Brain Res. 178: 555–566.PubMedCrossRefGoogle Scholar
  22. Olsen, R.W., 1982, Drug interactions at the GABA receptor-ionophore complex, Ann. Rev. Pharmacol. Toxiol. 22: 245–277.CrossRefGoogle Scholar
  23. Pannula, P., Yang, H-Y.T., Costa, E., 1984, Coexistence of Met5-enkephalin-Arg6-Phe7 with Met5-enkephalin and the possible role of Met5-enkephalin-Arg6-Phe7 in neuronal function, in: Coexistence of Neuroactive substances in Neurons, V. Chan-Palay and S.L. Palay ed., John Wiley and Sons, Inc., pp. 113–126, 1984.Google Scholar
  24. Pernow, B., 1983, Substance P, Pharmacol. Rev. 35: 85–141.PubMedGoogle Scholar
  25. Polc, P. and Haefely, W., 1976, Effects of two benzodiazepines, phenobarbitone and baclofen on synaptic transmission in the cate cuneate nucleus, Naunyn-Schmiedeberg Ach. Pharmacol. 294: 121–131.CrossRefGoogle Scholar
  26. Role, L.W., Leeman, S.L. and Perlman, R.L., 1981, Somatostatin and substance P inhibit catecholamine secretion from isolated cells of guinea-pig adrenal medulla, Neuroscience 6: 1813–1821.PubMedCrossRefGoogle Scholar
  27. Role, L.W., 1984, Substance P modulation of acetylcholine-induced currents in embryonic chicken sympathetic and ciliary ganglion neurons, Proc. Natl. Acad. Sci. 81: 2924–2928.PubMedCrossRefGoogle Scholar
  28. Saiani, L. and Guidotti, A., 1982, Opiate receptor-mediated inhibition of catecholamine release in primary cultures of bovine adrenal chromaffin cells, J. Neurochem. 39: 1669–1676.PubMedCrossRefGoogle Scholar
  29. Schultzberg, M., Lundberg, J.M., Hokfelt, T., Terenius, L., Brandt, J., Elde, R.P. and Goldstein, M., 1978, Enkephalin-like immunoreactivity in gland cells and nerve terminals of the adrenal medulla, Neuroscience 3: 1169–1186.PubMedCrossRefGoogle Scholar
  30. Stallcup, W.B. and Patrick, J., 1980, Substance P enhances cholinergic receptor desensitization in a clonal nerve cell line, Proc. Natl. Acad. Sci., 77: 634–638.PubMedCrossRefGoogle Scholar
  31. Stephenson, F.A., Casalotti, 0., Mamalaki, C. and Barnard, E.A., 1986, Antibodies recognising the GABAA/Benzodiazepine receptor including its regulatory sites, J. Neurochem. 46: 854–861.Google Scholar
  32. Suzdak, P.D., Schwartz, R.D., Skolnick, P. and Paul, S.M., 1986, Ethanol stimulates γ-aminobutyric acid receptor-mediated chloride transport in rat brain synaptoneurosomes, Proc. Natl. Acad. Sci. 83: 4071 - 4075.PubMedCrossRefGoogle Scholar
  33. Tatemoto, K., 1982, Neuropeptide Y: Complete amino acid sequence of the brain peptide, Proc. Nat. Acad. Sci. 79: 5485–5489.PubMedCrossRefGoogle Scholar
  34. Wojcik, W.J. and Neff, N.H., 1984, Gamma aminobutyric acid B receptors are negatively coupled to adenylate cyclase in brain, and in the cerebellum these receptors may be associated with granule cells, Mol. Pharmacol. 25: 24–28.PubMedGoogle Scholar
  35. Yang, H-Y.T., Hexum, T. and Costa, E., 1980, Opioid peptides in adrenal gland, Life Sci. 27: 1119–1125.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • E. Costa
    • 1
  • I. Hanbauer
    • 2
  • A. Guidotti
    • 1
  1. 1.Fidia-Georgetown Institute for the NeurosciencesUSA
  2. 2.Hypertension, Endocrine BranchNHLBI National Institute of HealthBethesdaUSA

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