Abstract
An investigation of the effects of a number of inositol trisphosphate analogues on the transient kinetics of Ca2+ release from cerebellar microsomes was undertaken. All the analogues investigated could release the total Ca2+ content of the inositol 1, 4,5-trisphosphate (Ins(1,4,5)P3) mobilizable Ca2+ store; however, their potencies were substantially reduced compared to Ins(1,4,5)P3. The concentration required to induce half-maximal Ca2+ mobilization was 0.14 microM for Ins(1,4,5)P3, 1.8 microM for 3-deoxyinositol 1,4, 5-trisphosphate (3-deoxyInsP3), 1.0 microM for 2,3-dideoxyinositol 1, 4,5-trisphosphate (2,3-dideoxyInsP3), 24 microM for 2,3, 6-trideoxyinositol 1,4,5-trisphopshate (2,3,6-trideoxyInsP3), and 2.9 microM for inositol 2,4,5-trisphosphate (Ins(2,4,5)P3). In all cases and for all concentrations tested, the inositol trisphosphate analogues induced biphasic transient release of Ca2+, which could fit to a biexponential equation assuming two independent processes. The rate constants calculated for the release process were much larger for Ins(1,4,5)P3 than the other inositol trisphosphates (the fast phase rate constant varying from 0.3 to 1.6 s-1 and the slow phase from 0.01-0.5 s-1, at concentrations between 0.03 and 20...Continue Reading
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