1. In addition to his many fine contributions in furthering our understanding of the neurochemical action of ecosanoids, catchelomines, steroids, anandamines, cannabinoids, endorphins, and the many modifications made to these neural factors, twenty years ago Julius Axelrod published a noteworthy paper concerning the nature of neuropeptides and their potential for multiple neurophysiological effects (Redgate et al., 1986).
2. In that report, Axelrod and coworkers described the neurological actions of the then recently discovered leucine- and methionine-enkephalins, and their biological functions which were novel, atypical, and in possession of neurological effects that were significantly “much more than additive.”
3. In this short communication I would like to expand on this observation concerning the “additive effects” contained within the amino acid sequence of the atypical neurotransmitter peptides leucine- and methonine-enkephalin.
Similar content being viewed by others
REFERENCES
Bradbury, A. F., Smyth, D. G., and Snell, C. R. (1976). Biosynthetic origin and receptor conformation of methionine enkephalin. Nature 260:165–166.
Childers, S. R., Creese, I., Snowman, A. M., and Synder, S.H. (1979). Opiate receptor binding affected differentially by opiates and opioid peptides. Eur. J. Pharmacol. 55:11–18.
Coupar, I. M. (1995). The peristaltic reflex in the rat ileum: Evidence for functional mu- and delta-opiate receptors. J. Pharm. Pharmacol.. 47:643–646.
Dores, R. M., Lecaude, S., Bauer, D., and Danielson, P. B. (2002). Analyzing the evolution of the opioid/orphanin gene family. Mass Spectrom. Rev. 21:220–243.
Hambrook, J. M., Morgan, B. A., Rance, M. J., and Smith, C. F. (1976). Mode of deactivation of the enkephalins by rat and human plasma and rat brain homogenates. Nature 262:782–783.
Hiroi, N., Martin, A. B., Grande, C., Alberti, I., Rivera, A., and Moratalla, R. (2002). Molecular dissection of dopamine receptor signaling. J. Chem. Neuroanat. 23:237–242.
Hughes, J., Smith, T. W., Kosterlitz, H. W., Fothergill, L. A., Morgan, B. A., and Morris, H. R. (1975). Identification of two related pentapeptides from the brain with potent opiate agonist activity. Nature 258:577–580.
Ikemoto, K. (2002). Human striatal D-neurons and their significance. Nihon Shinkei Seishin Yakurigaku Zasshi. 22:131–135.
Iversen, L. L., Kelly, J. S., Minchin, M., Schon, F., and Snodgrass, S. R. (1973). Role of amino acids and peptides in synaptic transmission. Brain Res. 62:567–576.
Janecka, A., Fichna, J., and Janecki, T. (2004). Opioid receptors and their ligands. Curr. Top. Med. Chem. 4:1–17.
Malfroy, B., Swerts, J. P., Guyon, A., Roques, B. P., and Schwartz J. C. (1978). High-affinity enkephalin-degrading peptidase in brain is increased after morphine. Nature 276:523–526.
McGeer, P. L., and McGeer, E. G. (1978). Aging and neurotransmitter systems. Adv. Exp. Med. Biol. 113:41–57.
Redgate, E. S., Deupree, J. D., and Axelrod, J. (1986). Interaction of neuropeptides and biogenic amines on cyclic adenosine monophosphate accumulation in hypothalamic nuclei. Brain Res. 365:61–69.
Roques, B. P. (2000). Novel approaches to targeting neuropeptide systems. Trends Pharmacol Sci. 21:475–483.
Simantov, R., and Snyder, S. H. (1976). Morphine-like peptides in mammalian brain: isolation, structure elucidation, and interactions with the opiate receptor. Proc. Natl. Acad. Sci. USA. 73:2515–2519.
Salvadori, S., and Temussi, P. A. (2004). Antagonism in opioid peptides: the role of conformation. Curr. Top. Med. Chem. 4:145–157.
Sokolov, O. Y., Kurasova, O. B., Kost, N. V., Gabaeva, M. V., Korneeva, E. V., Mikheeva, I. G., and Zozulya, A. A. (2004). Half-life of leu-enkephalin in the serum of infants of the first year of life on different types of feeding. Bull. Exp. Biol. Med. 137:342–344.
Snyder, S. H. (2004). Opiate receptors and beyond: 30 years of neural signaling research. Neuropharmacology 47:274–285.
Snyder, S. H., and Childers, S. R. (1979). Opiate receptors and opioid peptides. Annu. Rev. Neurosci. 2:35–64.
Tebecis, A. K. (1973). Transmitters and reticulospinal neurons. Exp. Neurol. 40:297–308.
Ungerstedt, U. (1971). Stereotaxic mapping of the monoamine pathways in the rat brain. Acta. Physiol. Scand. Suppl. 367:1–48.
Vogel, Z., and Altstein, M. (1980). Inactivation of enkephalin by brain enzymes. Prog. Biochem. Pharmacol. 16:49–59.
von Dorsche, H. H., Fehrmann, P., and Sulzmann, R. (1970). The mast cell as a unicellular endocrine gland. Acta Anat (Basel) 77:560–569.
ACKNOWLEDGMENTS
Thanks are extended to Aileen I. Pogue for the assembling and proofreading of this manuscript. This work was supported in part by NIA AG18031.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lukiw, W.J. Endogenous Signaling Complexity in Neuropeptides- Leucine- and Methionine-Enkephalin. Cell Mol Neurobiol 26, 1001–1008 (2006). https://doi.org/10.1007/s10571-006-9100-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10571-006-9100-6