PEPTIDE PROBES OF THE 5HT1A RECEPTOR G PROTEIN INTERFACE

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Serotonin receptors are involved in many aspects of human health and disease. The long-term goals of our work are to study the molecular pharmacology of these receptors, particularly emphasizing the interactions between serotonin receptors and a significant cellular signal transducing system, the G protein system. In the present project, we propose studies with a type of human serotonin receptor known as the 5HT1a receptor. This receptor belongs to a large superfamily of receptors which includes other important model receptors such as adrenergic and muscarinic cholinergic receptors. Based upon known characteristics of these model receptors, specific peptides representing biologically important regions of the 5HT1a receptor will be synthesized by solid phase methods. These peptides will then be directed against membrane-bound as well as solubilized human 5HT1a receptor. Interference with receptor-G protein interactions will be measured by agonist inhibition assays and by measuring effects on the second messenger cyclic AMP. Information gained from these studies will contribute to understanding the biology and structure of this receptor system, and may contribute to development of novel therapeutic drugs. Additionally, results may contribute in a more general manner to the model systems of the superfamily of receptors.