We report the discovery of a new CRF 2 receptor splice isoform found in human brain, which we have termed the CRF 2 � receptor. The CRF 2 � cDNA encodes for a 397-amino acid receptor that has an amino terminus with no significant homology to the already reported �- and �-termini. When expressed in 293-EBNA (Epstein-Barr nuclear antigen) cells, the CRF 2 � 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 EC 50 values more similar to CRF 2 � than CRF 2�. Equilibrium saturation isotherm analysis with radiolabeled sauvagine reveals a two site/state model for binding to CRF 2 � witha60pM K d highaffinity site anda5nM K d low-affinity site. Analysis of CRF 2 � RNA expression in human brain demonstrates expression in septum and hippocampus, with weaker but detectable expression in amygdala, nucleus accumbens, midbrain, and frontal cortex. (Molecular Endocrinology 12: 1077–1085, 1998)
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W. A. Kostich (1998) studied this question.