Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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.

Type

Journal article

Journal

Biochem J

Publication Date

01/08/1988

Volume

253

Pages

901 - 905

Keywords

Calcium, Cell Line, Dose-Response Relationship, Drug, Inositol, Inositol 1,4,5-Trisphosphate, Inositol Phosphates, Intracellular Fluid, Organothiophosphorus Compounds, Stereoisomerism, Sugar Phosphates, Tumor Cells, Cultured