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Molecular Endocrinology 12 (8): 1077-1085
Copyright © 1998 by The Endocrine Society

Molecular Identification and Analysis of a Novel Human Corticotropin-Releasing Factor (CRF) Receptor: The CRF2{gamma} Receptor

Walter A. Kostich1, Airu Chen1, Karen Sperle and Brian L. Largent

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{gamma} receptor. The CRF2{gamma} cDNA encodes for a 397-amino acid receptor that has an amino terminus with no significant homology to the already reported {alpha}- and ß-termini. When expressed in 293-EBNA (Epstein-Barr nuclear antigen) cells, the CRF2{gamma} 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{alpha} than CRF. Equilibrium saturation isotherm analysis with radiolabeled sauvagine reveals a two site/state model for binding to CRF2{gamma} with a 60 pM Kd high-affinity site and a 5 nM Kd low-affinity site. Analysis of CRF2{gamma} 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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