Research Project
3504389
Molecular cloning and heterologous expression of neurotransmitter receptor genes provides a means to study these sites of drug action free from the complexities of intact neural tissue. These heterologous expression systems can then be used as assay systems in the development of new therapeutic agents. Recently, a genomic clone for the serotonin 5-HT1A receptor was reported. This receptor has been associated with several central and peripheral nervous system actions including anxiety, thermoregulation and hypotension. Although the transfected 5-HT1A receptor has been studied by ligand binding approaches, functional expression of this cloned gene has not been demonstrated. On a second messenger level, the 5-HT1A receptor has been associated with both activation and inhibition or adenylate cyclase activity. The goal of this proposal is to transfect the 5-HT1A receptor gene into suitable mammalian cell hosts for the study of its functional coupling to the adenylate cyclase second messenger system. This heterologous expression system can then be used as a functional assay for the development of new therapeutic agents for the treatment of anxiety or other disease states involving 5-HT1A receptors. In addition, this expression system for receptors coup-ed to Gi-proteins can easily be applied to the functional assay of other cloned neurotransmitter receptor genes.
