Bombesin-induced cytosolic Ca2+ spiking in pancreatic acinar cells depends on cyclic ADP-ribose and ryanodine receptors.
Different hormones and neurotransmitters, using Ca2+ as their intracellular messenger, can generate specific cytosolic Ca2+ signals in different parts of a cell. In mouse pancreatic acinar cells, cytosolic Ca2+ oscillations are triggered by activation of acetylcholine (ACh), cholecystokinin (CCK) and bombesin receptors. Low concentrations of these three agonists all induce local Ca(2+)spikes, but in the case of bombesin and CCK these spikes can also trigger global Ca2+ signals. Here we monitor cytosolic Ca2+ oscillations induced by low (2-5 pM) concentrations of bombesin and show that, like ACh- and CCK-induced oscillations, the bombesin-elicited responses are inhibited by ryanodine(50 microM). We then demonstrate that, like CCK- but unlike ACh-induced oscillations, the responses to bombesin are abolished by intracellular infusion of the cyclic ADP ribose (cADPr) antagonist 8-NH2-cADPr (20 microM). We conclude that in mouse pancreatic acinar cells, bombesin, CCK and ACh all produce local Ca2+ spikes by recruiting common oscillator units composed of ryanodine and inositol trisphosphate receptors. However, bombesin and CCK also recruit cADPr receptors, which may account for the global Ca2+ signals that can be evoked by these two agonists. Our new results indicate that each Ca2+ -mobilizing agonist, acting on mouse pancreatic acinar cells, recruits a unique combination of intracellular Ca2+ channels.
Burdakov
D
D
MRC Secretory Control Research Group, The Physiological Laboratory, University of Liverpool, Crown Street, Liverpool, L69 3BX, UK
Cancela
J M
JM
Petersen
O H
OH
D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D036563:Cyclic ADP-Ribose; D051379:Mice; D010179:Pancreas / Q000502:physiology*; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D019837:Ryanodine Receptor Calcium Release Channel; D036563:Cyclic ADP-Ribose; D000246:Adenosine Diphosphate Ribose; D002118:Calcium