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.
Kostich
W A
WA
DuPont Merck Research Laboratories, CNS Diseases Research, Wilmington, Delaware 19880, USA.
Chen
A
A
Sperle
K
K
Largent
B L
BL
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