The neurotransmitter serotonin exerts diverse physiological effects in the central and peripheral nervous systems and in smooth muscle by interacting with specific membrane receptors. Serotonin receptors are the targets of many clinically important drugs. These receptors are classified into pharmacologically distinct subtypes, and some of the subtypes have been cloned recently. This proposal is for a molecular analysis of one subtype, the serotonin 1c receptor from the mouse brain. The receptor mRNA will be synthesized from the cDNA clones by in vitro transcription and will be injected into Xenopus oocytes for functional expression. Electrophysiological methods will be used to characterize the receptor function and to examine the changes in its function resulted from structural modifications. Several drugs, some of which are used clinically for neurological and psychiatric treatments, will be used to study their effects on receptor function. The possibility of a novel mechanism for the receptor-effector coupling will also be examined. In addition, the extra hydrophobic domain of the receptor, a unique feature of this receptor of the 17-helix"""""""" G protein-coupled receptor family, will be analyzed in detail to determine its functional significance. Also will be studied are the receptor desensitization and its influence on the receptor-mediated signal transduction. These studies will establish an understanding of the function of the serotonin 1c receptor at the molecular level, and will contribute to our knowledge of the receptor's role in bodily function.
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