Specificity of Phospholipase D Activation by Cholecystokinin and Phorbol Myristate Acetate but Not by Carbamylcholine and A23187 in Rat Pancreatic Acini

Abstract

The gastrointestinal hormone cholecystokinin and the muscarinic agonist carbamylcholine are involved in pancreatic enzyme secretion through phospholipase C activation and production of the second messengers inositol trisphosphate and diacylglycerol. However, cholecystokinin induces growth of the pancreas whereas carbamylcholine does not. This study investigated the possibility of a specific cellular signalling transduction system through which cholecystokinin may induce pancreatic growth. Rat pancreatic acini were preincubated with ³H choline or ³H myristic acid to label phosphatidylcholine. They were then stimulated by caerulein, phorbol myristate acetate, and carbamylcholine; choline and phosphocholine release as well as phosphatidic acid and phosphatidylethanol production were measured to establish phospholipase D (PLD) activation. Caerulein, phorbolester and carbamylcholine increased phosphocholine release. Choline release was induced early by caerulein and later by phorbolester but not by carbachol. PLD was activated by caerulein and phorbolester but not by carbamylcholine. Increased intracellular calcium by A23187 had no effect on PLD activation but its chelation by BAPTA prevented caerulein-induced PLD activation. In conclusion, PLD seems to be selectively activated by caerulein and phorbol ester by two different mechanisms which are insensitive to carbamylcholine. It is suggested that the PLD pathway might be the cellular signalling system leading to pancreatic growth.

Rat pancreatic acinar cells express a cytosolic phospholipase D1b isoform that is not regulated by cholecystokinin

“…However, it is not clear whether this process involves the activation of PLD by CCK or the presence of a constitutively active PLD. The finding that CCK is unable to increase PLD activity in intact acinar cells is in contradiction to earlier reports [13,14,15]. At present, however, we have no adequate explanation for this discrepancy.…”

“…Evidence for the involvement of PtdCho-PLD in CCK-induced diacylglycerol formation is the demonstration that the CCK analogue caerulein increases PLD activity in rat pancreatic acini [13,14,15]. PLD activity was assayed by means of the transphosphatidylation reaction [16].…”

Effects of the type of dietary fat on acetylcholine-evoked amylase secretion and calcium mobilization in isolated rat pancreatic acinar cells

“…Thus, whereas both ACh-and CCK-elicited Ca 2+ signaling are completely dependent on both IP3 and ryanodine receptors, the response induced by CCK (but not ACh) is also dependent on nicotinic acid adenine dinucleotide phosphate and cyclic ADP-ribose [20]. In addition, CCK (and not ACh) can activate phospholipase D [39].…”

Duck Pancreatic Acinar Cell as a Unique Model for Independent Cholinergic Stimulation–Secretion Coupling

“…In addition, CCK could activate calcium-dependently phospholipase D in rat pancreatic acinar cells, but cholinergic agonists could not (Rydzewska and Morisset 1995). Both local and global calcium signaling induced by ACh and CCK were different in rodents (Yule et al 1991).…”