Neurotransmitters, neuropeptides and hormones regulate a large number of physiological responses through their interaction with specific receptors. It is the activated receptor which initiates the intracellular events which finally causes the physiological response. The receptor is, therefore, at the center of all neuronal activities and its mode of action is basic to our understanding of mental health. Many different receptors exist. In the last two years, the successful cloning of some of them has led to the proposition of a new concept regarding their multiplicity. This concept states that although each neuroreceptor is different in its primary amino acid sequence, all the neuroreceptors can be classified into two classes, the ligand-gated ion channels and the G protein-coupled receptors. The receptors in these two classes share significant degree of sequence similarity and the same membrane topology, they are members of two large gene families. The G protein-coupled receptors constitute a predominant class of neuroreceptors, from which several members have already been cloned. Using a technical strategy based on the sequence similarities expected to exist between the G protein-coupled receptors, we have cloned and sequenced a new receptor which has all the characteristics of a G protein-coupled receptor. This receptor is expressed in the brain, in the pituitary, in the kidney but not in several peripheral organs such as the liver. This receptor has several characteristics of the dopamine D2 receptor. We propose to reach two major goals: the first is to find the ligand specificity of this receptor and the other is to perform a molecular study of this receptor to establish the foundations on which its structure-activities relationships can be analyzed.
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