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The hypocretins: Hypothalamus-specific peptides with neuroexcitatory activity

  1. J. G. Sutcliffe*
  1. Departments of *Molecular Biology and Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037; ‡Center for Sleep and Circadian Neurobiology, Stanford University, Stanford, CA 94305; §Department of Neurosurgery, Yale University, New Haven, CT 06520; ‖Institute of Basic Medical Sciences, Department of Biochemistry, University of Oslo, P.O. Box 1112, Blindern, N-0317 Oslo, Norway; and **The Jackson Laboratory, Bar Harbor, ME 04609

  1. Contributed by F. E. Bloom

Abstract

We describe a hypothalamus-specific mRNA that encodes preprohypocretin, the putative precursor of a pair of peptides that share substantial amino acid identities with the gut hormone secretin. The hypocretin (Hcrt) protein products are restricted to neuronal cell bodies of the dorsal and lateral hypothalamic areas. The fibers of these neurons are widespread throughout the posterior hypothalamus and project to multiple targets in other areas, including brainstem and thalamus. Hcrt immunoreactivity is associated with large granular vesicles at synapses. One of the Hcrt peptides was excitatory when applied to cultured, synaptically coupled hypothalamic neurons, but not hippocampal neurons. These observations suggest that the hypocretins function within the CNS as neurotransmitters.

Footnotes

    • ↵† L.d.L. and T.S.K. contributed equally to this paper.

    • Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. AF019565 and AF019566).

  • ABBREVIATION

    Hcrt,
    hypocretin
    • Accepted November 17, 1997.

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