A primary focus of this program is the interaction of neural and respiratory tissues. Neurotransmitter receptors, in addition to their pivotal role in cell-to-cell communication within the confines of the central nervous system, serve as the interface between neural and respiratory elements. It is, therefore, appropriate that as the aims of the individual projects progress towards the molecular level of analysis during the renewal period that receptor proteins are the first molecular element within physiological control pathways to be selected for study. Characterization of the role of receptors in the physiological processes which serve as the focus of the overall proposal will pave the way to future studies at the molecular level, including second messengers, protein phosphorylation, and gene regulation. Receptor studies will provide a point of entry for the extension of current lines of inquiry into the molecular realm. The molecular pharmacology core is designed to provide data on the characteristics and distribution of neurotransmitter receptors in the CNS and the periphery which are relevant and useful for the progress of the individual projects of the program. Membrane binding assays and quantitative receptor autoradiography will be performed by core personnel in a central laboratory using advanced equipment already on hand. The core director, co-investigators and consultants all have extensive experience in the experimental analysis of receptor recognition sites. The director will be responsible for overseeing the operation of the core and reporting results back to the primary investigators. As an additional service, the core will advise investigators concerning the use of pharmacological tools to manipulate physiological systems and provide a central repository of bioactive compounds (a """"""""drug library"""""""") for use by individual investigators. This service will eliminate duplicate ordering of bioactive agents and assure proper storage and dating. The expense and professional effort necessary to provide these services is only a small fraction of the costs which would be incurred if each investigator in the program were to set up receptor pharmacological methods in his laboratory, purchase necessary equipment and supplies, and acquire experience in the design and interpretation of receptor binding assays.
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