Sustained Ca2+ signaling in mouse lacrimal acinar cells due to photolysis of "caged" glycerophosphoryl-myo-inositol 4,5-bisphosphate.
In saponin-permeabilized mouse lacrimal acinar cells, glycerophosphoryl-myo-inositol 4,5-bisphosphate (GPIP2) activated the release of sequestered Ca2+ to the same extent as inositol 1,4,5-trisphosphate ((1,4,5)IP3) but with a potency about 1/10 that of (1,4,5)IP3. In lacrimal gland homogenates, [3H]GPIP2 was metabolized to two compounds which upon anion exchange high performance liquid chromatography eluted at positions indicating that they were [3H]GPIP and [3H]GPIP3. The rate of metabolism of [3H]GPIP2 was much slower than that of [3H](1,4,5)IP3, and its rate of phosphorylation was less than 1% of that of [3H] (1,4,5)IP3. In intact lacrimal cells, photolysis of a microinjected "caged" derivative of GPIP2, 1-(alpha-glycerophosphoryl)-myo-inositol 4,5-bisphosphate P4(5)-1-(2-nitrophenyl)ethyl ester, resulted in sustained activation of Ca2+ signaling; i.e. intracellular Ca2+ release followed by increased entry of Ca2+ across the plasma membrane. These findings indicate that caged GPIP2 should provide a useful tool for producing photolytically initiated, sustained activation of intracellular (1,4,5)IP3 receptors. They also provide strong support for the idea that sustained Ca2+ signaling can be achieved in lacrimal acinar cells by activation of intracellular receptors for (1,4,5)IP3 in the absence of stimulated production of inositol 1,3,4,5-tetrakisphosphate.
Bird
G S
GS
Calcium Regulation Section, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709.
Obie
J F
JF
Putney
J W
JW
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D007295:Inositol Phosphates / Q000378:metabolism*; D007700:Kinetics; D007765:Lacrimal Apparatus / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000378:metabolism*; D010766:Phosphorylation; D010782:Photolysis; D012503:Saponins; D015398:Signal Transduction; D013997:Time Factors; D014316:Tritium
D007295:Inositol Phosphates; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D012503:Saponins; D014316:Tritium; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium