In permeabilized lacrimal acinar cells, cyclic ADP-ribose (cADP-ribose) and inositol 1,4,5-trisphosphate (Ins(1,4,5)P-3) release Ca2+ in a dose dependent manner from distinct thapsigargin-sensitive Ca2+ pools. Ryanodine specifically blocks the Ca2+ response to cADP-ribose, whereas heparin strongly reduces the response to Ins(1,4,5)P-3 application. GTP causes a rapid Ca2+ release by a ryanodine- and heparin-insensitive mechanism and potentiates Ins(1,4,5)P-3 but not cADP-ribose evoked Ca2+ release. It is estimated that cADP-ribose can release 16 mu mol Ca2+/l tells, whereas Ins(1,4,5)P-3 can mobilize 55 mu mol Ca2+/l cells. The results suggest that cADP-ribose and Ins(1,4,5)P-3 release Ca2+ from distinct internal stores and that a third Ca2+ pool exists which can selectively interact with the Ins(1,4,5)P-3-sensitive Ca2+ store by a GTP-mediated process.
