Cited by 3,878Sleep and Wakefulness ResearchRegulation of Appetite and ObesityNeuropeptides and Animal Physiology

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The hypocretins: Hypothalamus-specific peptides with neuroexcitatory activity

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de Lecea, L., Kilduff, T. S., Peyron, C., Gao, X.-B., Foye, P. E., Danielson, P. E., Fukuhara, C., Battenberg, E. L. F., Gautvik, V. T., Bartlett, F. S., Frankel, W. N., van den Pol, A. N., Bloom, F. E., Gautvik, K. M., Sutcliffe, J. G.·1998·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.95.1.322PMC PMC18213

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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.

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The Rat Brain in Stereotaxic Coordinates
Paxinos, G., & Watson, C. (1983) · Elsevier eBooks · doi:10.1016/c2009-0-63235-9 · Cited by 28,585
AChE-stained horizontal sections of the rat brain in stereotaxic coordinates
Paxinos, G., WATSON, C. R. R., & Emson, P. C. (1980) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(80)90021-7 · Cited by 4,501
Targeted disruption of the melanocortin-4 receptor results in obesity in mice
Huszar, D., Lynch, C. A., Fairchild-Huntress, V., Dunmore, J. H., Fang, Q., Berkemeier, L. R., Gu, W., Kesterson, R. A., Boston, B. A., Cone, R. D., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)81865-6 · Cited by 3,030
Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein
Ollmann, M. M., Wilson, B. D., Yang, Y.-K., Kerns, J. A., Chen, Y., Gantz, I., & Barsh, G. S. (1997) · Science · doi:10.1126/science.278.5335.135 · Cited by 1,881
Brain Maps: Structure of the Rat Brain
Swanson, L. W. (1992) · Medical Entomology and Zoology · Cited by 1,878
Brain maps: structure of the rat brain
Guillery, R. W. (1993) · Trends in Neurosciences · doi:10.1016/0166-2236(93)90187-q · Cited by 1,669
A role for melanin-concentrating hormone in the central regulation of feeding behaviour
Qu, D., Ludwig, D. S., Gammeltoft, S., Piper, M., Pelleymounter, M. A., Cullen, M. J., Mathes, W. F., Przypek, J., Kanarek, R. B., & Maratos–Flier, E. (1996) · Nature · doi:10.1038/380243a0 · Cited by 1,320
NEUROPEPTIDE Y AND HUMAN PANCREATIC POLYPEPTIDE STIMULATE FEEDING BEHAVIOR IN RATS
Clark, J. T., Kalra, P. S., Crowley, W. R., & Kalra, S. P. (1984) · Endocrinology · doi:10.1210/endo-115-1-427 · Cited by 1,276
Localization of the melanocortin-4 receptor (MC4-R) in neuroendocrine and autonomic control circuits in the brain
Mountjoy, K. G., Mortrud, M. T., Low, M. J., Simerly, R. B., & Cone, R. D. (1994) · Molecular Endocrinology · doi:10.1210/mend.8.10.7854347 · Cited by 1,157
Corticotropin-releasing factor-producing neurons in the rat activated by interleukin-1
Berkenbosch, F., van Oers, J., del Rey, A., Tilders, F., & Besedovsky, H. (1987) · Science · doi:10.1126/science.2443979 · Cited by 1,151

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Research works printed but not linked: 4

L W Swanson Handbook of Chemical Anatomy, eds A Bjorkland, T Hokfelt, L W Swanson (Elsevier, New York) 5, 1–124 (1987).
G P Smith, J Gibbs Pharmacol Biochem Behav 3, 135–138 (1975).
K Arase, D A York, H Shimizu, N Shargill, G A Bray Am J Physiol 255, E255–E259 (1988).
K G Mountjoy, M T Mortrud, M J Low, R B Simerly, R D Cone Mol Endocrinol 8, 1298–1308 (1994).

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Winsky-Sommerer, R., Yamanaka, A., Diano, S., Borok, E., Roberts, A. J., Sakurai, T., Kilduff, T. S., Horvath, T. L., & de Lecea, L. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.3459-04.2004 · Cited by 462
The role of orexin in motivated behaviours
Sakurai, T. (2014) · Nature reviews. Neuroscience · doi:10.1038/nrn3837 · Cited by 478
Gene expression and protein distribution of the orexin-1 receptor in the rat brain and spinal cord
Hervieu, G. J., Cluderay, J. E., Harrison, D. C., Roberts, J. C., & Leslie, R. A. (2001) · Neuroscience · doi:10.1016/s0306-4522(01)00033-1 · Cited by 463
Ghrelin-Induced Food Intake Is Mediated via the Orexin Pathway
Toshinai, K., Date, Y., Murakami, N., Shimada, M., Mondal, M. S., Shimbara, T., Guan, J., Wang, Q., Funahashi, H., Sakurai, T., et al. (2003) · Endocrinology · doi:10.1210/en.2002-220788 · Cited by 470
Role of neuropeptides in appetite regulation and obesity – A review
Arora, S., & Anubhuti, A. (2006) · Neuropeptides · doi:10.1016/j.npep.2006.07.001 · Cited by 471
Low cerebrospinal fluid hypocretin (orexin) and altered energy homeostasis in human narcolepsy
Nishino, S., Ripley, B. A., Overeem, S., Nevšímalová, S., Lammers, G. J., Vaňková, J., Okun, M. L., Rogers, W. M., Brooks, S. N., & Mignot, E. J.-M. (2001) · Annals of Neurology · doi:10.1002/ana.1130 · Cited by 451
Fluctuation of extracellular hypocretin‐1 (orexin A) levels in the rat in relation to the light–dark cycle and sleep–wake activities
Yoshida, Y., Fujiki, N., Nakajima, T., Ripley, B. A., Matsumura, H., Yoneda, H., Mignot, E. J.-M., & Nishino, S. (2001) · European Journal of Neuroscience · doi:10.1046/j.0953-816x.2001.01725.x · Cited by 449
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Garland, T., Schutz, H., Chappell, M. A., Keeney, B. K., Meek, T. H., Copes, L. E., Acosta, W., Drenowatz, C., Maciel, R. C., van Dijk, G., et al. (2011) · Journal of Experimental Biology · doi:10.1242/jeb.048397 · Cited by 444
The hypocretin/orexin ligand–receptor system: implications for sleep and sleep disorders
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The effect of the orexins on food intake: comparison with neuropeptide Y, melanin-concentrating hormone and galanin
Edwards, C., Abusnana, S., Sunter, D., Murphy, K. G., Ghatei, M. A., & Bloom, S. R. (1999) · Journal of Endocrinology · doi:10.1677/joe.0.160r007 · Cited by 433
Characterization of CART neurons in the rat and human hypothalamus
Elias, C. F., Lee, C. E., Kelly, J. F., Ahima, R. S., Kuhar, M. J., Saper, C. B., & Elmquist, J. K. (2001) · The Journal of Comparative Neurology · doi:10.1002/cne.1085 · Cited by 433
Obesity and the Hypothalamus: Novel Peptides for New Pathways
Flier, J. S., & Maratos–Flier, E. (1998) · Cell · doi:10.1016/s0092-8674(00)80937-x · Cited by 430
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Sutcliffe, J. G., & de Lecea, L. (2002) · Nature reviews. Neuroscience · doi:10.1038/nrn808 · Cited by 416
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Motivational activation: a unifying hypothesis of orexin/hypocretin function
Mahler, S. V., Moorman, D. E., Smith, R. J., James, M. H., & Aston‐Jones, G. (2014) · Nature Neuroscience · doi:10.1038/nn.3810 · Cited by 392
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Kenny, P. J. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn3105 · Cited by 382
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Cox, C. D., Breslin, M. J., Whitman, D. B., Schreier, J. D., McGaughey, G. B., Bogusky, M. J., Roecker, A. J., Mercer, S. P., Bednar, R. A., Lemaire, W., et al. (2010) · Journal of Medicinal Chemistry · doi:10.1021/jm100541c · Cited by 381
Orexin Receptors: Pharmacology and Therapeutic Opportunities
Scammell, T. E., & Winrow, C. J. (2011) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010510-100528 · Cited by 391
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Nishino, S., & Kanbayashi, T. (2005) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2005.03.004 · Cited by 376
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Goadsby, P. J., Charbit, A. R., Andreou, A. P., Akerman, S., & Holland, P. R. (2009) · Neuroscience · doi:10.1016/j.neuroscience.2009.03.019 · Cited by 380
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Zigman, J. M., & Elmquist, J. K. (2003) · Endocrinology · doi:10.1210/en.2003-0241 · Cited by 382

Authors: de Lecea, L., Kilduff, T. S., Peyron, C., Gao, X.-B., Foye, P. E., Danielson, P. E., Fukuhara, C., Battenberg, E. L. F., Gautvik, V. T., Bartlett, F. S., Frankel, W. N., van den Pol, A. N., Bloom, F. E., Gautvik, K. M., & Sutcliffe, J. G.
Affiliations: 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
Scripps Research Institute (US)
ORCID: Kilduff, T. S.
Peyron, C.
Gao, X.-B.
Gautvik, V. T.
Frankel, W. N.
Gautvik, K. M.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 1998-01-06
Volume: 95
Issue: 1
Pages: 322-327
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.95.1.322
PMC: PMC18213
OpenAlex: W2152211310
Cited by: 3,878
References: 46
Citations by year: 2026: 83 · 2025: 126 · 2024: 108 · 2023: 123 · 2022: 156 · 2021: 133 · 2020: 137 · 2019: 133 · 2018: 170 · 2017: 159 · 2016: 159 · 2015: 173 · 2014: 208 · 2013: 186 · 2012: 188
FWCI: 55.05
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
Funders: Fondation Fyssen
Norges Forskningsråd
National Institutes of Health (5r01ns033396-03, 5p01ag011084-05)
National Institute on Aging (AG-11084)
National Institute of General Medical Sciences (GM-32355, R01GM032355)
National Institute of Neurological Disorders and Stroke (NS33396)
Army Research Office
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords: orexin, hypothalamus, hypothalamic neurons, secretin, neuropeptides, neurotransmitters, hypothalamic projections, brainstem, thalamus
MeSH terms: Orexins, Amino Acid Sequence, Animals, Base Sequence, Carrier Proteins, Chromosomes, Homeostasis, Hypothalamus, Posterior, Male, Molecular Sequence Data, Neurons, Neuropeptides, Protein Precursors, Secretin, Synaptic Vesicles, Consensus Sequence, Rats, Wistar, Neurotransmitter Agents, Intracellular Signaling Peptides and Proteins, Mice, Rats

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The hypocretins: Hypothalamus-specific peptides with neuroexcitatory activity

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