Semisynthetic derivatives of inositol 1,4,5-trisphosphate substituted at the 1-phosphate group. Effects on calcium release from permeabilized guinea-pig parotid acinar cells and comparison with binding to aldolase A.

Derivatives of inositol 1,4,5-(tris)phosphate [Ins(1,4,5)P3] substituted at phosphate 1 were compared with respect to their calcium releasing effect in permeabilized guinea pig parotid acinar cells and to their inhibitory action on aldolase A. sn-Glycero(3)-1-phospho-D-myo-inositol-4,5-(bis)phosphate, but also glycolaldehyde(2)-1-phospho-D-myo-inositol-4,5-(bis)phosphate [GcaPIns(4,5)P2] and its derivative N-octyl-aminoethanol(1)-1-phospho-D-myo-inositol-4,5-(bis)phosphate stimulated calcium release and inhibited aldolase A. The relative efficacy of the different derivatives of Ins(1,4,5)P3 was similar for both effects. N-Hydroxyethyl-2-aminoethanol(1)-1-phospho-D-myo-inositol-4,5-(bis)phosp hate [HeAetPIns(4,5)P2], another derivative of GcaPIns(4,5)P2 was considerably less effective on both parameters than the other Ins(1,4,5)P3 derivatives. Although the concentration leading to half-maximal activation of calcium release varied from 1.7 microM for Ins(1,4,5)P3 to 128 microM for HeAetPIns(4,5)P2, the maximal effect was the same for all derivatives. The results indicate that the 1-phosphate group of Ins(1,4,5)P3 can be modified without or with only minor loss of biological activity. This may be utilized for future studies aiming at elucidating the putative Ins(1,4,5)P3 binding site.