Abstract
This chapter presents an overview of recent progress in corticotropin-releasing factor (CRF) receptor agents. CRF is a neurohormone that appears necessary and sufficient for the organism to mount functional, physiological and endocrine responses to stressors. CRF receptors belong to the family of “gut-brain” neuropeptide receptors. Other typical members of this family are receptors for calcitonin, vasoactive intestinal peptide, parathyroid hormone, secretin, pituitary adenylate cyclase-activating peptide, glucagon, and growth hormone-releasing factor. The chapter documents recent progress toward the goal of assigning functional significance to endogenous CRF circuits in brain. It examines the state of the art regarding the growing array of pharmacological tools, including the most recently published small-molecule ligands, which are available for further probing the physiological significance of CRF system activation. Concepts related to functional significance of CRF receptors and CRF-binding protein are described. CRF binding-protein (CRF-BP) is described and CRF mutant mouse models are analyzed. CRF gene knockdown is elaborated and a discussion on human stress-axis pathophysiology is presented. CRF receptor and CRF-BP selective pharmacological tools are reviewed and details of construction of CRF peptide analogs are provided. Concepts related to in vivo efficacy profile of CRF receptor and CRFBP ligands are also discussed in the chapter.
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