Molecular biology of the CRH receptors-- in the mood.
Dysfunctioning of corticotropin-releasing hormone (CRH) and its receptors (CRH(1) and CRH(2)) has been linked to the development of stress-related disorders, such as mood and eating disorders. The molecular characterization of CRH(1) and CRH(2) receptors and their splice variants has generated detailed information on their pharmacology, tissue distribution and physiology. While mammalian CRH(1) receptors nonselectively bind CRH analogs, the ligand specificity of CRH(2) is narrower. CRH(1) receptors are predominantly expressed in the brain and pituitary, whereas CRH(2) receptor expression is limited to particular brain areas and to some peripheral organs. Molecular approaches to block CRH(1) receptor expression in the brain argue in favor of its involvement in the regulation of some aspects of the stress response. The CRH(2alpha) receptor may be more important for motivational types of behavior essential for survival, such as feeding and defense.(1)
Dautzenberg
F M
FM
F. Hoffmann-La Roche Ltd., Pharma Division, Preclinical Research Grenzacher Strasse 124, 4070, Basel, Switzerland. frank.dautzenberg@roche.com
Kilpatrick
G J
GJ
Hauger
R L
RL
Moreau
J
J
D000339:Affect / Q000502:physiology; D017398:Alternative Splicing; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D051379:Mice; D008822:Mice, Transgenic; D010902:Pituitary Gland / Q000737:chemistry; D017434:Protein Structure, Tertiary; D051381:Rats; D018019:Receptors, Corticotropin-Releasing Hormone / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D008024:Ligands; D018019:Receptors, Corticotropin-Releasing Hormone; D003346:Corticotropin-Releasing Hormone