Urocortin II: a member of the corticotropin-releasing factor (CRF) neuropeptide family that is selectively bound by type 2 CRF receptors.
Here we describe the cloning and initial characterization of a previously unidentified CRF-related neuropeptide, urocortin II (Ucn II). Searches of the public human genome database identified a region with significant sequence homology to the CRF neuropeptide family. By using homologous primers deduced from the human sequence, a mouse cDNA was isolated from whole brain poly(A)(+) RNA that encodes a predicted 38-aa peptide, structurally related to the other known mammalian family members, CRF and Ucn. Ucn II binds selectively to the type 2 CRF receptor (CRF-R2), with no appreciable activity on CRF-R1. Transcripts encoding Ucn II are expressed in discrete regions of the rodent central nervous system, including stress-related cell groups in the hypothalamus (paraventricular and arcuate nuclei) and brainstem (locus coeruleus). Central administration of 1-10 microg of peptide elicits activational responses (Fos induction) preferentially within a core circuitry subserving autonomic and neuroendocrine regulation, but whose overall pattern does not broadly mimic the CRF-R2 distribution. Behaviorally, central Ucn II attenuates nighttime feeding, with a time course distinct from that seen in response to CRF. In contrast to CRF, however, central Ucn II failed to increase gross motor activity. These findings identify Ucn II as a new member of the CRF family of neuropeptides, which is expressed centrally and binds selectively to CRF-R2. Initial functional studies are consistent with Ucn II involvement in central autonomic and appetitive control, but not in generalized behavioral activation.
Reyes
T M
TM
Laboratory of Neuronal Structure and Function, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Lewis
K
K
Perrin
M H
MH
Kunitake
K S
KS
Vaughan
J
J
Arias
C A
CA
Hogenesch
J B
JB
Gulyas
J
J
Rivier
J
J
Vale
W W
WW
Sawchenko
P E
PE
D000595:Amino Acid Sequence; D000818:Animals; D001522:Behavior, Animal; D016466:CHO Cells; D003001:Cloning, Molecular; D003346:Corticotropin-Releasing Hormone / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006224:Cricetinae; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D054832:Urocortins; D000099052:CRF Receptor, Type 1
C101531:CRF receptor type 2; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; C518358:urocortin 2, mouse; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone