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 u nidentified CRF-related neuropeptide, urocortin II (Ucn II). Searches of th e public human genome database identified a region with significant sequenc e homology to the CRF neuropeptide family. By using homologous primers dedu ced from the human sequence, a mouse cDNA was isolated from whole brain pol y(A)(+) RNA that encodes a predicted 38-aa peptide, structurally related to the other known mammalian family members, CRF and Ucn. Ucn II binds select ively 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 th e rodent central nervous system, including stress-related cell groups in th e hypothalamus (paraventricular and arcuate nuclei) and brainstem (locus co eruleus). Central administration of 1-10 mug of peptide elicits activationa l responses (Fos induction) preferentially within a core circuitry subservi ng autonomic and neuroendocrine regulation, but whose overall pattern does not broadly mimic the CRF-R2 distribution. Behaviorally, central Ucn II att enuates nighttime feeding, with a time course distinct from that seen in re sponse to CRF. In contrast to CRF, however, central Ucn II failed to increa se gross motor activity. These findings identify Ucn II as a new member of the CRF family of neuropeptides, which is expressed centrally and binds sel ectively to CRF-R2. Initial functional studies ape consistent with Ucn II i nvolvement in central autonomic and appetitive control, but not in generali zed behavioral activation.