Synergistic effects of inositol 1,3,4,5-tetrakisphosphate on inositol 2,4,5-trisphosphate-stimulated Ca2+ release do not involve direct interaction of inositol 1,3,4,5-tetrakisphosphate with inositol trisphosphate-binding sites

We have previously found that for permeabilized L1210 cells, low micromolar concentrations of Ins(1,3,4,5)P % added prior to Ins(2,4,5)P $ enhance the effects of suboptimal concentrations of Ins(2,4,5)P $ in causing Ca#+ release from InsP $ -sensitive Ca#+ stores [Cullen, Irvine and Dawson (1990) Biochem. J. 271, 549–553]. If this was due either to some conversion of added Ins(1,3,4,5)P % into Ins(1,4,5)P $ by the 3-phosphatase, or to Ins(1,3,4,5)P % acting as a weak (or partial) agonist on the InsP $ receptor it would be expected that, in the presence of thimerosal to sensitize the InsP $ receptor, the dose–response curve to Ins(1,3,4,5)P % would be left-shifted by the same extent as that of Ins(1,4,5)P $ . This was found not to be the case ; the dose–response curve to Ins(1,3,4,5)P % was not shifted at all by thimerosal.