G-protein Coupled Glutamate Receptors
Introduction Glutamate plays a major, widespread role in the control of neuroendocrine neurons, possibly controlling not only the neuroendocrine system but other hypothalamic regions as well. There are four major subclasses of glutamate receptor, one of which is coupled to a membrane-bound, GTP-binding protein (the G protein) and is pharmacologically and functionally distinct from the other major glutamate receptors (the G protein-coupled glutamate receptor, or GluG R.). Technology description The invention provides isolated and substantially pure preparations of mammalian G protein-coupled glutamate receptors and fragments. In preferred embodiments the receptors are coupled to a G protein in vertebrate cells, bind glutamate and quisqualate and thereby activate phospholipase C, and are capable of stimulating inositol phospholipid metabolism. Having provided these in isolated and purified form, the invention also provides antibodies to the receptor in the form of antisera and/or monoclonal antibodies. In another aspect the invention provides the ability to produce the mammalian G proteincoupled glutamate receptor and polypeptides or fragments thereof by recombinant means, preferably in cultured eukaryotic cells. In related embodiments the invention concerns DNA constructs which comprise a transcriptional promoter, a DNA sequence which encodes the receptor or fragment, and a transcriptional terminator, each operably linked for expression of the receptor (for expression the construct may also contain at least one signal sequence.)
The constructs are ideally used to transform or transfect eukaryotic cells, preferably mammalian cells which do not express endogenous G protein-coupled glutamate receptors. Cells which express the G protein-coupled glutamate receptors may also be used to identify compounds which can alter the receptor-mediated metabolism of a eukaryotic cell. In further embodiments the invention relates to methods for diagnosis, where the presence of a mammalian G protein-coupled glutamate receptor in a biological sample may be determined. Business Opportunity This technology has applications in drug screening and pharmacology. It can be used to identify new drugs and screen libraries of compounds for effect on this receptor, and to screen and develop new agonists and/or antagonists specific for GluG R. Intellectual Property Position Many US patents have issued and more are pending both in the US and internationally.
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