Type 3 inositol 1,4,5-trisphosphate receptor modulates cell death

Mechanisms accounting for the cellular entry of calcium that mediates cellu lar proliferation and apoptosis have been obscure. Previously we reported s elective augmentation of type 3 inositol (1,4,5) trisphosphate receptors (I P(3)R3) in lymphocytes undergoing programmed cell death, which was prevente d by antisense constructs to IP(3)R3. We now report increases in mRNA and p rotein levels for IP(3)R3 associated with cell death in several apoptotic p aradigms in diverse tissues. Elevations of IP,RS occur during developmental apoptosis in early postnatal cerebellar granule cells, dorsal root gang-li a, embryonic hair follicles, and intestinal villi. Neurotoxic damage elicit ed by the glutamate agonist kainate is also associated with IP(3)R3 augment ation. In chick dorsal root ganglia neurons undergoing apoptosis due to dep rivation of nerve growth factor, levels of IP(3)R3 are selectively increase d and cell death is selectively prevented by antisense oligonucleotides to IP(3)R3. Thus, IP(3)R3 appears to participate actively in cell death in a d iversity of tissues.