Research Project
2272230
Alpha adrenoceptors serve numerous functions throughout the peripheral and central nervous systems. Chemical modulators of these receptors have a variety of potential therapeutic applications, including treatments for benign prostatic hyperplasia, hypertension, pain and glaucoma. Although six alpha adrenoceptor subtypes are now known, little information is available concerning the locations and physiological functions of these subtypes in the body. The three-dimensional structures of these receptors, and the chemical nature of their interactions with ligands are also poorly understood. Ligands were identified by our cloned human receptor screening program which bind selectively to individual alpha adrenoceptor subtypes. In Phase I, some of these compounds will be used as templates for the design of new pharmacological tools. These tools will include molecules that selectively inactivate one subtype by covalent modification, as well as subtype-selective radioligands. In Phase I and II, these new pharmacological tools will be used to determine the localization and functional capabilities of the different alpha adrenergic subtypes in various human and animal tissues. These tools will also be useful for structural characterization of the receptor-ligand complexes. Information obtained in these studies will aid the identification of new therapeutic opportunities and the design of new drugs.
