Stereospecific mobilization of intracellular Ca2+ by inositol 1,4,5-triphosphate. Comparison with inositol 1,4,5-trisphosphorothioate and inositol 1,3,4-trisphosphate - PubMed (original) (raw)

Stereospecific mobilization of intracellular Ca2+ by inositol 1,4,5-triphosphate. Comparison with inositol 1,4,5-trisphosphorothioate and inositol 1,3,4-trisphosphate

J Strupish et al. Biochem J. 1988.

Abstract

The stereo specificity of myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] to mobilize Ca2+ from an intracellular store has been examined in permeabilized rat pituitary-tumour GH3 and Swiss 3T3 cells. A comparison of D-Ins(1,4,5)P3 with the synthetic enantiomer L-Ins(1,4,5)P3 and the racemate DL-Ins(1,4,5)P3 clearly demonstrates the marked stereospecificity of the response. Whereas D-Ins(1,4,5)P3 released 30-50% of non-mitochondrially-bound Ca2+ with a EC50 (concentration producing 50% of maximal response) of 200 nM, the L isomer was both substantially less potent and efficacious. A high concentration of the L isomer (10 microM) did not significantly shift the dose-response curve for the D isomer in Swiss 3T3 cells, suggesting that the less active isomer is probably a very weak agonist. Other studies revealed, in contrast with previous work, that the other naturally occurring isomer, D-Ins(1,3,4)P3, was essentially inactive in releasing Ca+, whereas a novel 5-phosphatase-resistant analogue, DL-myo-inositol 1,4,5-trisphosphorothioate, was a relatively potent full agonist in GH3 cells. These data reveal, for the first time, the stereoselectivity of the intracellular receptor associated with Ca2+ release. They also provide evidence for the activity of the novel phosphorothioate analogue of Ins(1,4,5)P3, but suggest that D-Ins(1,3,4)P3 is not involved in cellular Ca2+ mobilization.

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Stereospecific mobilization of intracellular Ca2+ by inositol 1,4,5-triphosphate. Comparison with inositol 1,4,5-trisphosphorothioate and inositol 1,3,4-trisphosphate - PubMed (original) (raw)