INTERACTIONS BETWEEN INOSITOL TRIS-PHOSPHATES AND TETRAKIS-PHOSPHATES - EFFECTS ON INTRACELLULAR CA2+ MOBILIZATION IN SH-SY5Y CELLS

The potential Ca2+-releasing activity of the inositol tetrakisphosphates Ins(1,3,4,6)P4 and DL-Ins(1,4,5,6)P4 and the inositol pentakisphosphate Ins(1,3,4,5,6)P5 and their effect on Ins(1,4,5)P3- and DL-Ins(1,3,4,5)P4-mediated Ca2+ release were examined in permeabilized SH-SY5Y human neuroblastoma cells. Neither DL-Ins(1,4,5,6)P4 nor Ins(1,3,4,5,6)P5 exhibit Ca2+-releasing activity at concentrations up to 10-mu-M, but Ins(1,3,4,6)P4 releases Ca2+ dose-dependently, with an EC50 value (concn. giving half-maximal effect) of 5.92 +/- 0.47-mu-M. Maximal response by this tetrakisphosphate (49 +/- 2.5%) is significantly less than that seen with Ins(1,4,5)P3 (60 +/- 3 %) and is achieved at a concentration of 30-mu-M. In the presence of this concentration of Ins(1,3,4,6)P4 the EC50 value for Ins(1,4,5)P3-mediated Ca2+ release increases from 0.12 +/- 0.02-mu-M to 2.11 +/- 0.51-mu-M, providing evidence that this naturally occurring inositol tetrakisphosphate may recognize and exhibit its Ca2+-releasing activity via the Ins(1,4,5)P3 receptor. DL-Ins(1,3,4,5)P4, however, at its maximally effective concentration (10-mu-M) does not significantly affect Ins(1,4,5)P3-mediated Ca2+ release, and therefore appears to mediate its Ca2+-mobilizing action through a receptor distinct from that for Ins(1,4,5)P3.