Cholecystokinin-evoked Ca(2+) waves in isolated mouse pancreatic acinar cells are modulated by activation of cytosolic phospholipase A(2), phospholipase D, and protein kinase C.
We employed confocal laser-scanning microscopy to monitor cholecystokinin (CCK)-evoked Ca(2+) signals in fluo-3-loaded mouse pancreatic acinar cells. CCK-8-induced Ca(2+) signals start at the luminal cell pole and subsequently spread toward the basolateral membrane. Ca(2+) waves elicited by stimulation of high-affinity CCK receptors (h.a.CCK-R) with 20 pM CCK-8 spread with a slower rate than those induced by activation of low-affinity CCK receptors (l.a. CCK-R) with 10 nM CCK-8. However, the magnitude of the initial Ca(2+) release was the same at both CCK-8 concentrations, suggesting that the secondary Ca(2+) release from intracellular stores is modulated by activation of different intracellular pathways in response to low and high CCK-8 concentrations. Our experiments suggest that the propagation of Ca(2+) waves is modulated by protein kinase C (PKC) and arachidonic acid (AA). The data indicate that h.a. CCK-R are linked to phospholipase C (PLC) and phospholipase A(2) (PLA(2)) cascades, whereas l.a.CCK-R are coupled to PLC and phospholipase D (PLD) cascades. The products of PLA(2) and PLD activation, AA and diacylglycerol (DAG), cause inhibition of Ca(2+) wave propagation by yet unknown mechanisms.
González
A
A
Faculty of Medicine, University of Saarland, Homburg/Saar, D-66421, Germany.
Schmid
A
A
Sternfeld
L
L
Krause
E
E
Salido
G M
GM
Schulz
I
I
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000201:enzymology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D010179:Pancreas / Q000378:metabolism*; D010739:Phospholipase D / Q000378:metabolism; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D011949:Receptors, Cholecystokinin / Q000502:physiology; D015398:Signal Transduction; D012844:Sincalide / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D011949:Receptors, Cholecystokinin; D016718:Arachidonic Acid; D011493:Protein Kinase C; D010741:Phospholipases A; D010739:Phospholipase D; D012844:Sincalide; D002118:Calcium