This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The last major part of the CART system to be identified is the CART receptor (it is possible that there are several receptors). Screening for medications related to CART peptides requires an ability to work with and express the receptor. While there have been several publications on the receptor, we have begun an intensive study with the goal of improving assays and a cloning of the receptor. The CART receptor binding assay has been standardized, and levels of specific binding in several cell lines have been measured. Specifically specific binding has been found in PC12 cells;when these cells differentiate, the binding increases. Microarray analysis has identified several possible receptors that are increased after differentiation and are therefore receptor candidates. Another approach to finding the CART peptide receptor has been to study known orphan receptors (an orphan is a receptor that is known, but whose activating substrate is unknown). Some orphan receptors have been expressed in cells, but as of this date, it is not yet clear if these are candidates. We continue to make significant progress identifying the CART peptide receptor(s).