cis,cis-Cyclohexane 1,3,5-triol polyphosphates release calcium from Neurospora crassa via an unspecific ins 1,4,5-P₃ receptor

We investigated the effects of new inositol 1,4,5-trisphosphate analogues on the release of Ca²⁺ from isolated vacuoles of Neurospora crassa. Tri-O-butyryl-inositol 1,4,5-trisphosphate and a set of cis,cis-cyclohexane 1,3,5-triol bis-(CHT-P₂) and trisphosphates (CHT-P₃) gave an increase in free Ca²⁺ as measured directly with fura-2, a Ca²⁺-chelator. However, inositol 1,4-bisphosphate, 6-O-palmitoyl-inositol 4,5-bisphosphate and trans-cyclohexane 1,2-diol bisphosphate (trans CHD-P₂) did not induce Ca²⁺-release. These results suggest that the 1,5-bisphosphate position in inositol 1,4,5-trisphosphate (Ins 1,4,5-P₃) is the only essential arrangement for receptor binding to vacuoles of Neurospora crassa. The structures of these analogues are discussed on the basis of a general concept for the design of new Ins 1,4,5-P₃ analogogues.