MONOCLONAL ANTIBODIES SPECIFIC FOR THE PARATHYROID HORMONE RECEPTOR

PARATHYROID HORMONE (PTH) PLAYS A CENTRAL ROLE IN THE CONTROL OF BONE AND MINERAL HOMEOSTASIS THROUGH ITS INTERACTION WITH SPECIFIC RECEPTORS IN TARGET TISSUES, INCLUDING BONE AND KIDNEY. THE COMBINED EFFECTS OF PTH ACTING THROUGH ITS SKELETAL AND RENAL RECEPTORS IS TO RAISE SERUM CALCIUM, STIMULATE COUPLED BONE TURNOVER, AND PROMOTE POSITIVE CALCIUM BALANCE. GIVEN THE KEY ROLE PTH PLAYS IN CALCIUM AND SKELETAL HOMEOSTASIS, IT IS OBVIOUS THAT PURIFICATION AND STRUCTURAL MAPPING OF THE RECEPTOR THROUGH WHICH IT MEDIATES ITS ACTIONS WOULD BE INSTRUMENTAL IN ADVANCING KNOWLEDGE OF THE MYRIAD OF DISEASE STATES INVOLVING ABNORMALITIES OF BONE TURNOVER. THE OVERALL GOAL OF THIS PROJECT IS TO DEVELOP A PANEL OF MONOCLONAL ANTIBODIES SPECIFIC FOR THE PTH RECEPTOR. IMMUNOGENS TO INDUCE THESE ANTIBODIES WILL CONSIST OF INTACTCELLS THAT EXPRESS RELATIVELY HIGH CONCENTRATIONS OF PTH RECEPTORS. THREE DIFFERENT CULTURED CELL LINES WILL BE USED: UMR-106 RAT OSTEOBLASTOMA CELLS, DIFFERENTIATED F9 MOUSE EMBRYONAL CARCINOMA CELLS, AND IMMORTALIZED OPOSSUM KIDNEY CELLS. THE AVAILABILITY OF MONOCLONAL ANTIBODIES SPECIFIC FOR THE PTH RECEPTOR WOULD BE USEFUL IN EFFORTS TO PURIFY AND CHARACTERIZE THE RECEPTOR AND COULD LEAD TO THE DEVELOPMENT OF USEFUL THERAPEUTIC AGENTS.