We are delighted that the excitatory neuropeptide modulators, which
we discovered and named the hypocretins (1), have attracted so much
attention of late, having been implicated as playing a role in the
suppression of entry to REM sleep (2), acting through at least one of
their receptors, the hypocretin 2 receptor. Although Joseph Takahashi's
perspective says that our structure for
hypocretin 1 deduced from its cDNA sequence was incorrect, we stated in our paper that the "N-terminal
extent of Hcrt1 is not established," and thus our structure for this
peptide was incomplete until Sakurai and colleagues (3) provided the
essential contribution of analyzing endogenous Hcrt1, thereby
elucidating fully its structure.
Takahashi further suggests that the hypocretin nomenclature "should
probably be reconsidered." The term hypocretin was originally coined to
reflect the exclusively hypothalamic origin of the peptides and their
sequence relationship to the secretin peptide family. With a number of
functional possibilities, few of which had been tested at the time, the
name hypocretin was endorsed by a survey of neuroscientists at the 1997
Society for Neuroscience Meeting (4) and was used by the OMIM and MGD
genetic databases, largely because of the temporal priority in the absence
of a singular biological or biochemical function. Sakurai and associates
subsequently named the same peptides orexins because of their evidence for
a role in feeding behavior, a clever term reflecting one activity of the
hypocretins, at least in rats. However, the anatomical distribution of
hypocretin-ergic synaptic terminals suggested roles for these peptides not
only in feeding, but also in the sleep-wake cycle, blood pressure
regulation, regulation of endocrine secretion, and thermoregulation
(1,4,5). During the past 2 years, experimental support for each of these
functions has indeed emerged (6). Thus, although unintentional, the term,
orexin, seems unnecessarily restrictive for a peptide system involved in
multiple homeostatic mechanisms. Moreover, Takahashi's suggestion,
narcoleptin, seems both premature and, again, overly restrictive in these
still early days. For these reasons we suggest that the original
definition, hypocretin, is still the most representative and appropriate
for this exciting, multifunctional family of peptides.
J. Gregor Sutcliffe, The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037,USA; Luis de Lecea, The Scripps Research Institute; Thomas S. Kilduff, SRI International, Menio Park, CA 94025, USA; Christelle Peyron, Stanford University, Stanford, CA 94305, USA; Pamela E. Foye, The Scripps Research Institute; Patria E. Danielson, The Scripps Research Institute; Wayne N. Frankel, The Jackson Laboratory, Bar Harbor, ME 04609, USA; Anthony N. van den Pol, Yale University, New Haven, CT 06529, USA; Vigdis T. Gautvik, University of Oslo, Norway; Kaare M. Gautvik, University of Oslo;Floyd E. Bloom, The Scripps Research Institute.
References and Notes
1. K. M. Gautvik et al., Proc. Natl. Acad. Sci. U.S.A. 93, 8733 (1996);
L. de Lecea et al., Proc. Natl. Acad. Sci. U.S.A. 95, 322 (1998).
2. L. Lin et al., Cell 98, 365 (1999); R. M. Chemelli et al., Cell 98, 437 (1999).
3. T. Sakurai et al., Cell 92, 573 (1998).
4. J. G. Sutcliffe et al., Soc. Neurosci. Abstr. 23, 2032 (1997); Peyron et al., ibid.
5. C. Peyron et al., J. Neurosci. 18, 9996 (1998).
6. A. N. van den Pol et al., J. Neurosci. 18, 7962 (1998); S. Pu et al., Regulatory Peptides 78, 133 (1998); W. K. Samson et al., Brain Res. 831, 248 (1999); J. J. Hagan et al., Proc. Natl. Acad. Sci. U.S.A. 96, 10911 (1999).
E-Letters: ![[Read E-Letter]](/icons/misc/sectionDOWN.gif){kind=icon}
