Agonist-stimulated pathways of calcium signaling in pancreatic acinar cells.
In pancreatic acinar cells stimulation of different intracellular pathways leads to different patterns of Ca2+ signaling. Bombesin induces activation of both phosphatidylinositol 4,5-bisphosphate (PIP2)-specific phospholipase C (PLC) and phospholipase D (PLD). The latter leads to generation of diacylglycerol (DAG) in addition to that produced by activation of PIP2-PLC. Strong activation of protein kinase C (PKC) results in inhibition of Ca(2+)-induced Ca2+ release from Ca2+ pools arranged in sequence to the luminally located IP3-sensitive Ca2+ pools. Consequently the Ca2+ wave which starts in the luminal cell pole is slower in the presence of bombesin (5 microm/s) as compared to that in the presence of acetylcholine (17 microm/s) which activates PIP2-PLC but not PLD. Activation of high-affinity CCK-receptors triggers a Ca2+ wave with slow propagation (5 microm/s) due to stimulation of phospholipase A2 (PLA2) and generation of arachidonic acid, which in turn leads to inhibition of Ca(2+)-induced Ca2+ release. Low-affinity CCK-receptors are coupled to both PIP2-PLC and PLD.
Schulz
I
I
II. Physiologisches Institut, Universität des Saarlandes, Homburg/Saar, Germany.
Krause
E
E
González
A
A
Göbel
A
A
Sternfeld
L
L
Schmid
A
A
D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001839:Bombesin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D002766:Cholecystokinin / Q000494:pharmacology; D036563:Cyclic ADP-Ribose; D004789:Enzyme Activation; D010179:Pancreas / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D011493:Protein Kinase C / Q000378:metabolism
D015220:Calcium Channels; D036563:Cyclic ADP-Ribose; D000246:Adenosine Diphosphate Ribose; D002766:Cholecystokinin; D011493:Protein Kinase C; D010741:Phospholipases A; D054467:Phospholipases A2; D001839:Bombesin; D002118:Calcium