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Receptor
DuPont Merck Research Laboratories CNS Diseases Research Wilmington, Delaware 19880
We report the discovery of a new
CRF2 receptor splice isoform found in human
brain, which we have termed the CRF2
receptor. The CRF2
cDNA encodes for a
397-amino acid receptor that has an amino terminus with no significant
homology to the already reported
- and ß-termini. When expressed
in 293-EBNA (Epstein-Barr nuclear antigen) cells, the
CRF2
receptor responds in a dose-dependent
manner to CRF and related peptides with a rank order of potency of
urocortin
sauvagine>urotensin>r/h CRF, with
EC50 values more similar to
CRF2
than CRF2ß.
Equilibrium saturation isotherm analysis with radiolabeled sauvagine
reveals a two site/state model for binding to
CRF2
with a 60 pM
Kd high-affinity site and a 5
nM Kd low-affinity
site. Analysis of CRF2
RNA expression in
human brain demonstrates expression in septum and hippocampus, with
weaker but detectable expression in amygdala, nucleus accumbens,
midbrain, and frontal cortex.
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