Dopamine D1 receptors appear to play a significant role in a number of medically important processes including: control of blood pressure, neurohypophyseal hormone release, retinal neuromodulation, natriuresis, gut motility and secretion, motor movement, emotions, behavior and the perceptual state of mind. In particular the dopaminergic system in the brain has been associated with the neurological and psychiatric disorders such as Parkinson's disease and schizophrenia. These receptors are difficult to study due to their low density and interference by other dopamine receptor sites. Since D1 receptors are important targets for new drug development initiatives, a program to clone these receptors and express them in heterologous expression systems has been taken. These expression systems will then be used as tools for the development of new therapeutic agents. In Phase I of this program, two separate human genes which code for receptors of the dopamine D1 pharmacological class were successfully isolated. One of these two receptors represents the fourth member of the dopamine receptor to be cloned. This receptor is a new member of the G protein-coupled receptor family and represents the first report of a gene encoding a functional G-protein coupled receptor accompanied by a closely related pseudogene. The cloning of this receptor, named D18, provides the first clear demonstration that subtypes of the human dopamine D1 receptors are present. In Phase II, the plan is to search for additional members of this new dopamine receptor family and initiate a drug development program focused on these two closely related human receptors.
