Specific binding sites for inositolhexakisphosphate in brain and anterior pituitary

[³H]Inositolhexakisphosphate (InsP₆) binds to a single population of specific and saturable recognition sites in membranes prepared from cerebral hemispheres, anterior pituitaries, or cultured cerebellar neurons. Binding is temperature and pH dependent, exhibits slow association and dissociation kinetics, and differentiates among various inositolpolyphosphates (InsP₆ is much more potent than inositol-1,3,4,5,6-pentakis- and inositol-1,3,4,5-tetrakisphosphate, whereas inositol-1,4,5-trisphosphate is inactive as a displacer). In membranes from cerebral hemispheres, saturation analysis reveals a K_D value of 33 ± 4 nM and a maximal density (B_max) of 152 ± 23 pmol/mg of protein. Both affinity and density of [³H]InSP₆ binding are lower in membranes from anterior pituitaries. In cultured cerebellar neurons, micromolar concentrations of divalent cations enhance both [³H]InsP₆ binding and InsP₆-stimulated ⁴⁵Ca²⁺ uptake, suggesting that activation of specific receptors may be involved in the stimulation of ⁴⁵Ca²⁺ uptake produced by InsP₆. These data support the recent view that InsP₆, as other inositolpolyphosphates, may act as a signal molecule in excitable cells.