MOLECULAR BIOLOGY OF NEUROTRANSMITTER RECEPTORS

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Recently, we published a paper on Cloning and Sequence Analysis of the Human Brain beta-Adrenergic Receptor (FEBS Lett. 211:200-206, 1987). In a recent review concerning the evolution of adrenergic and cholinergic receptors we further postulated that the muscarinic cholinergic receptor has existed for over 600 million years (Prog. Neurobiol., in press) Pharmacological and biochemical evidence suggests that the beta-adrenergic receptor appeared later in evolution raising the possibility that it evolved as a result of gene duplication. In order to further answer questions concerning receptor evoltion we are in the process of cloning beta-adrenergic and muscarinic cholinergic receptors from shark and Drosophila tissue. The cloning of neural receptor genes also allowed us to study the structure-function relationship of these receptors by site-directed mutagenesis. We have successfully expressed the human beta2-adrenergic receptor gene is a mouse cell line previously lacking the functional receptor. A series of single amino acid substitution mutants have also been made and are in the process of being characterized. Study of these mutants should help us to locate those important residues responsible for ligand binding, signal transduction or maintenance of structural integrity. *(Transferred from LNP on 7/87).