Molecular identification and analysis of a novel human corticotropin-releasing factor (CRF) receptor: the CRF2gamma receptor.
We report the discovery of a new CRF2 receptor splice isoform found in human brain, which we have termed the CRF2gamma receptor. The CRF2gamma cDNA encodes for a 397-amino acid receptor that has an amino terminus with no significant homology to the already reported alpha- and beta-termini. When expressed in 293-EBNA (Epstein-Barr nuclear antigen) cells, the CRF2gamma receptor responds in a dose-dependent manner to CRF and related peptides with a rank order of potency of urocortin > or = sauvagine>urotensin>r/h CRF, with EC50 values more similar to CRF2alpha than CRF2beta. Equilibrium saturation isotherm analysis with radiolabeled sauvagine reveals a two site/state model for binding to CRF2gamma with a 60 pM Kd high-affinity site and a 5 nM Kd low-affinity site. Analysis of CRF2gamma RNA expression in human brain demonstrates expression in septum and hippocampus, with weaker but detectable expression in amygdala, nucleus accumbens, midbrain, and frontal cortex.
DuPont Merck Research Laboratories, CNS Diseases Research, Wilmington, Delaware 19880, USA.
W A
WA
Kostich
A
A
Chen
K
K
Sperle
B L
BL
Largent
D000595:Amino Acid Sequence; D000679:Amygdala / Q000378:metabolism; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D002490:Central Nervous System / Q000378:metabolism; D003001:Cloning, Molecular; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007536:Isomerism; D008969:Molecular Sequence Data; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D014018:Tissue Distribution; D054832:Urocortins
D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; D003346:Corticotropin-Releasing Hormone