THE ROLE OF THE 2-HYDROXYL AND 3-HYDROXYL GROUPS OF 1D-MYO-INOSITOL 1,4,5-TRISPHOSPHATE IN THE MOBILIZATION OF CALCIUM FROM PERMEABILIZED HUMAN 1321N1 ASTROCYTOMA-CELLS

The functional significance of the 2- and 3-hydroxyl groups of 1D-myo-inositol 1.4,5-trisphosphate [Ins(1,4,5)P3] was probed by using Ins(1,4,5)P3 analogues variously modified at positions 2 and 3 or elsewhere. The intrinsic activities of these compounds were compared to that of Ins(1,4,5)P3, using the calcium-mobilising receptor of the 1321N1 human astrocytoma cell line. The ligand-binding affinities were also determined using membrane preparations from rat cerebellum and bovine adrenal-cortex. The results show that HO-2 and HO-3 of Ins(1,4,5)P3 have a relatively insignificant role in receptor binding and calcium release. However, the possibility of a regulatory role for the 3-position of Ins(1,4,5)P3 in these processes is proposed.