Phospholipid turnover in isolated rat pancreatic acini. Consideration of the relative roles of phospholipase A2 and phospholipase C.
The purpose of the present study was to explore the interaction of phosphatidylinositol breakdown and the turnover of arachidonic acid in isolated rat pancreatic acini by using receptor agonists and the calcium ionophore ionomycin. Acini prelabelled with myo-[(3)H]inositol in vivo responded to carbachol with a rapid breakdown of phosphatidylinositol. In the presence of [(32)P]P(i), carbachol increased labelling of phosphatidic acid and phosphatidylinositol within 1 and 5 min respectively. Carbachol also rapidly stimulated the incorporation of [(14)C]arachidonic acid into phosphatidylinositol within 2 min, and the peptidergic secretagogue caerulein caused the loss of radioactivity from phospholipids prelabelled with arachidonic acid. Ca(2+) deprivation partially impaired the stimulatory action of carbachol on arachidonic acid turnover. In contrast with its stimulatory effects on [(32)P]P(i) and [(14)C]arachidonate incorporation, carbachol inhibited the incorporation of the saturated fatty acid stearic acid into phosphatidylinositol. Whereas ionomycin stimulation of phosphatidylinositol breakdown and [(32)P]P(i) labelling of phospholipids was slower in onset and less effective than carbachol stimulation, the ionophore effectively promoted (arachidonyl) phosphatidylinositol turnover within 2 min. These results implicate two separate pathways for stimulated phosphatidylinositol degradation in the exocrine pancreas, involving phospholipases A(2) and C. Whereas mobilization of cellular Ca(2+) appears sufficient to cause activation of phospholipase A(2) and amylase secretion, additional events triggered by receptor activation may be required to act in concert with Ca(2+) to optimally stimulate phospholipase C. The nature of the interaction between phospholipases A(2) and C and their specific physiological roles in pancreatic secretion remain to be elucidated.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D004987:Ethers / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism; D066298:In Vitro Techniques; D015759:Ionomycin; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010740:Phospholipases / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D010738:Type C Phospholipases / Q000378:metabolism*
D001095:Arachidonic Acids; D004987:Ethers; D005227:Fatty Acids; D007476:Ionophores; D010743:Phospholipids; D016718:Arachidonic Acid; D015759:Ionomycin; D002217:Carbachol; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases