Developmental and adult expression of rat calcium-sensing receptor transcripts in neurons and oligodendrocytes

The calcium-sensing receptor (CaSR) is a member of a growing family of hept ahelical receptors with an unusually large extracellular domain. To further delineate its functions in neurons and glia, we have investigated the expr ession pattern of CaSR transcripts in the postnatal and adult rat brain, sp inal cord and dorsal root ganglia by in situ hybridization. CaSR-expressing cells were spatially and temporally regulated in myelinated structures wit h a caudo-rostral pattern that paralleled that of myelin basic protein, a m arker of myelination, with a downregulation observed in the adult. Double-l abelling studies demonstrated that CaSR mRNA colocalizes with myelin basic protein-expressing cells within fibre tracts, suggesting that CaSR is expre ssed by mature oligodendrocytes. In cultured rat oligodendrocytes, Ca2+ ind uced stimulation of phosphatidylinositol hydrolysis with an EC50 of 1.4 mm and increased intracellular calcium. NPS R-568 (1 mu m), a calcimimetic, si gnificantly stimulates the inositol phosphate response, whereas a less pote nt stereoisomer, NPS S-568 (1 mu m), was without effect. These data suggest that a functional CaSR is expressed in mature oligodendrocytes with a pote ntial role in myelination. CaSR expression was also developmentally regulat ed in neurons of the orbital cortex and in the CA2 region of the hippocampu s, and present in olfactory nuclei, hypothalamic areas and in the area post rema through postnatal days to adulthood. This expression is consistent wit h a role of CaSR in olfactory or gustatory signal integration, and with the regulation of fluid and mineral homeostasis. CaSR expression in a subpopul ation of small cells in dorsal root ganglia suggests additional roles for e xtracellular Ca2+ in sensory nerves.