AUTORADIOGRAPHIC LOCALIZATION OF CRF1 AND CRF2 BINDING-SITES IN ADULT-RAT BRAIN

The regional distribution of corticotropin-releasing factor(1) (CRF1) and CRF2 binding sites was assessed autoradiographically in adult rat brain. The differential pharmacological profiles of the CRF1 and CRF2 receptor subtypes were used for the discrimination of the CRF1 and CRF 2 receptor subtypes in rat brain. Pharmacological characterization at the human CRF1 receptor subtype, expressed in baculovirus-infected Sf9 cells, showed high affinity binding (Ki less than or equal to 10.0 nM ) for the peptide agonists sauvagine, urotensin I, rat/human CRF, and ovine CRF. Pharmacological characterization at the rat CRF2 receptor s ubtype expressed in CHO cells showed a rank order affinity for the pep tide agonists such that sauvagine, urotensin I and rat/human CRF showe d high affinity binding whereas ovine CRF had a Ki value of 300 nM. Ba sed on this differential binding affinity for ovine CRF, [I-125] sauva gine binding in the presence of increasing concentrations of ovine CRF was used to discriminate CRF1 from CRF2 receptor subtypes in rat brai n. The CRF1 receptor subtype was found to be localized to various regi ons of the cerebellum, as well as to several cortical areas. The CRF2 receptor subtype was shown to be localized to the lateral septal nucle us, entorhinal cortex, and to amygdaloid and hypothalamic regions. The present autoradiographic findings provide evidence that each subtype has a distinct regional distribution, thus strengthening the suggestio n that CRF1 and CRF2 receptors serve different roles in mediating CRF function. Such data suggest that the development of CRF receptor subty pe selective antagonists should help to delineate the role of CRF1 and CRF2 receptor subtypes in central nervous system function. (C) 1997 A merican College of Neuropsychopharmacology. Published by Elsevier Scie nce Inc.