Lymphocyte apoptosis: Mediation by increased type 3 inositol 1,4,5-trisphosphate receptor

B and T lymphocytes undergoing apoptosis in response to anti-immunoglobulin M antibodies and dexamethasone, respectively, were found to have increased amounts of messenger RNA for the inositol 1,4,5-trisphosphate receptor (IP(3)R) and increased amounts of IP(3)R protein. Immunohistochemical analysis revealed that the augmented receptor population was localized to the plasma membrane. Type 3 IP(3)R (IP(3)R3) was selectively increased during apoptosis, with no enhancement of type 1 IP(3)R (IP(3)R1). Expression of IP(3)R3 antisense constructs in S49 T cells blocked dexamethasone-induced apoptosis, whereas IP(3)R3 sense, IP(3)R1 sense, or IP(3)R1 antisense control constructs did not block cell death. Thus, the increases in IP(3)R3 may be causally related to apoptosis.