Camp-Stimulatory Serotonin Receptors

Activation of a subset of serotonin receptors evokes physiological responses characteristic ofadenylate cyclase stimulation in a wide variety of tissues: neuronal depolarization, relaxation of smoothmuscle, and positive inotropy in cardiac muscle. The receptor subtypes will serve as drug targets forpotential therapeutic roles in irritable bowel disease, postoperative ileus, diabetic gastroparesis, emesis,achalasia, hiatal hernia, esophageal spasm, angina, coronary artery disease, atherosclerosis, stroke, anddisorders of higher cognitive processes. Despite the obvious medical significance of this subfamily ofserotonin receptors which couple to the to the activation of adenylate cyclase, the molecularcharacterization of the family of serotonin receptors coupled to activation of adenylate cyclase has notbeen well documented. Phase I will attempt to identify members of this family and to characterize thetissue distribution of these receptors. Such information should provide valuable data on the physiologicalresponses to serotonin activation which are coupled to increase in cAMP. In Phase II, we shall initiatea drug development program which focuses on designing receptor-specific compounds.