This proposal addresses the Molecular Neurobiology interest of NINDS from the latest Omnibus solicitation. A high throughput, fluorescence based technique to measure receptor mediated cellular responses is proposed. The goal is to develop an optical probe capable of measuring intracellular Ca2+ signals reported by fluorescent dyes for high volume application such as screening a number of synthetic or natural compounds. A number of reporter dyes are now available to measure intracellular Ca2+ signals following surface membrane receptor activation and methods exist to test if these signals are transduced by inotropic or metabotropic mechanisms. The optical probe design will incorporate efficient light throughput, cell perfusion and fast data acquisition. The commercial application of the development is that a rapid, inexpensive and quantitative assay will become available to be offered as a contract service by Receptor Biology to pharmaceutical companies, government and universities to screen novel synthetic and naturally occurring compounds in the search for novel neuro-active pharmaceuticals. The major advantage of the method include: 1) independence from radioisotopes; 2) independence from laboratory animals; 3) rapidity, simplicity and low cost; 4) high volume throughput; 5) quantitative measure of receptor occupancy and efficacy; 6) adaptable to hundreds of receptors and subtypes.
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