Novel CRF--Receptor

Corticotropin releasing factor (CRT), a 41 amino acid peptide, controls the anterior pituitary secradrenocorticotropin and other proopiomelanocortin products. CRT also coordinates the endocrine, behaautonomic responses to stress. Recent clinical data suggest that CRT may be of relevance to endocrinneurologic illness. A CRT receptor (CRT-lR) which is expressed in the pituitary gland and is widelyrecently been cloned and functionally expressed. While many of the effects of CRT in brain may be methere are some discrepancies between the distribution of CRT-1R and the sites of action of the neuropresence of additional CRT receptor subtype(s). For example, many of the autonomic, behavioral and eCRT have been localized in hypothalamus; however, there is a paucity of CRT-1R in this brain area. Hshowing the existence of a second CRT-receptor (CRT- 2R) isolated from rat hypothalamus. PreliminaryCRT-2R indicates significant differences from CRT-1R in sequence, tissue distribution and pharmacoloSpecifically, the CRT-2R shows significant expression in the hypothalamus and lateral septum but onlexpression levels in pituitary. In an attempt to understand the relevance of the novel CRT-2R to thepathological actions of CRT, we will 1) clone the human equivalent of the CRT- 2R; 2) establish stabthe rat and human CRT-2R; 3) determine the pharmacologic profile of the CRT-2R in radioligand bindinmessenger assays; 4) determine the tissue distribution of CRT- 2R mRNA in rat and human brain by in5) carry out a preliminary survey on the behavioral effects of CRT and related peptides microinjecteenriched with CRT-2R.