INTRACELLULAR GLUCOSE SWITCHES BETWEEN CYCLIC ADP-RIBOSE AND INOSITOLTRISPHOSPHATE TRIGGERING OF CYTOSOLIC CA2+ SPIKING

Cyclic ADP-ribose (cADPR) is a potentially important intracellular Ca2 + releasing messenger [1-5]. In pancreatic acinar cells where intracel lular infusion of both inositol trisphosphate (IP3) and cADPR evoke re petitive Ca2+ spiking [6], the cADPR antagonist 8-NH2-cADPR [7], which blocks cADPR-evoked but not IF, evoked Ca2+ spiking, can abolish Ca2 spiking induced by physiological levels of the peptide hormone cholec ystokinin (CCK) [8]. We have tested the effect of intracellular glucos e on the ability of IP3, cADPR and CCK to induce cytosolic Ca2+ spikes in pancreatic acinar cells. In order to gain access to the intracellu lar cytosol, we used the whole-cell configuration of the patch-clamp t echnique [9] and monitored cytosolic Ca2+ concentration changes by mea suring the Ca2+-dependent ionic current [10-13]. Glucose (300 mu M to 10 mM) in the patch pipette/intracellular solution prevented cADPR fro m evoking Ca2+ spiking. The same effect was observed with P-deoxy-gluc ose, but not L-glucose. In contrast, glucose potentiated IP3-evoked Ca 2+ spiking. CCK evoked Ca2+ spiking irrespective of the presence or ab sence of intracellular glucose, but the cADPR antagonist 8 NH, cADPR b locked CCK-evoked Ca2+ spiking only in the absence of intracellular gl ucose, This suggests that the hormone can evoke Ca2+ spiking via eithe r the IP3 or the cADPR pathway. The intracellular glucose level may co ntrol a switch between these two pathways.