Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior.
The hypothalamus plays a central role in the integrated control of feeding and energy homeostasis. We have identified two novel neuropeptides, both derived from the same precursor by proteolytic processing, that bind and activate two closely related (previously) orphan G protein-coupled receptors. These peptides, termed orexin-A and -B, have no significant structural similarities to known families of regulatory peptides. prepro-orexin mRNA and immunoreactive orexin-A are localized in neurons within and around the lateral and posterior hypothalamus in the adult rat brain. When administered centrally to rats, these peptides stimulate food consumption. prepro-orexin mRNA level is up-regulated upon fasting, suggesting a physiological role for the peptides as mediators in the central feedback mechanism that regulates feeding behavior.
Sakurai
T
T
Howard Hughes Medical Institute, Department of Molecular Genetics, University of Texas Southwestern Medical Center at Dallas, 75235-9050, USA.
Amemiya
A
A
Ishii
M
M
Matsuzaki
I
I
Chemelli
R M
RM
Tanaka
H
H
Williams
S C
SC
Richardson
J A
JA
Kozlowski
G P
GP
Wilson
S
S
Arch
J R
JR
Buckingham
R E
RE
Haynes
A C
AC
Carr
S A
SA
Annan
R S
RS
McNulty
D E
DE
Liu
W S
WS
Terrett
J A
JA
Elshourbagy
N A
NA
Bergsma
D J
DJ
Yanagisawa
M
M
D000818:Animals; D016466:CHO Cells; D002352:Carrier Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D005215:Fasting / Q000502:physiology; D005247:Feeding Behavior / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D007031:Hypothalamus / Q000737:chemistry* / Q000166:cytology; D047908:Intracellular Signaling Peptides and Proteins; D007668:Kidney / Q000166:cytology; D008297:Male; D008969:Molecular Sequence Data; D009474:Neurons / Q000737:chemistry / Q000187:drug effects; D009479:Neuropeptides / Q000235:genetics* / Q000302:isolation & purification / Q000494:pharmacology; D064446:Orexin Receptors; D000068797:Orexins; D011498:Protein Precursors / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification; D017386:Sequence Homology, Amino Acid
D002352:Carrier Proteins; C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D011498:Protein Precursors; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D019204:GTP-Binding Proteins