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.
Laboratory of Neuronal Structure and Function, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
T M
TM
Reyes
K
K
Lewis
M H
MH
Perrin
K S
KS
Kunitake
J
J
Vaughan
C A
CA
Arias
J B
JB
Hogenesch
J
J
Gulyas
J
J
Rivier
W W
WW
Vale
P E
PE
Sawchenko
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