Analysis of the regulation of phosphatidylinositol-4,5-bisphosphate synthesis by arachidonic acid in exocrine pancreas.
In pancreatic acinar cells prelabeled with either 32Pi or myo-[3H]inositol, arachidonic acid (10-50 microM) rapidly decreased the steady-state levels of [32P]phosphatidylinositol 4',5'-bisphosphate [( 32P]PtdIns4,5P2) and inhibited carbachol-stimulated accumulation of [3H]inositol trisphosphate [( 3H]InsP3). Both actions of arachidonic acid were rapidly reversed by bovine serum albumin (BSA). Indomethacin and nordihydoguaiaretic acid failed to block the inhibitory effects of arachidonic acid on [32P]PtdIns4,5P2 levels. Arachidonic acid (10-50 microM) also caused a prompt depletion of cellular ATP which was rapidly reversed by BSA. The ATP-depleting action of arachidonate paralleled in terms of concentration dependence and time course its inhibitory effects on [32P]PtdIns4,5P2 and [3H]InsP3 levels. Exposure of acinar cells to 50 microM arachidonic acid produced an increase in oxygen consumption which exceeded that elicited by either carbachol or ionomycin. Arachidonic acid (10-50 microM) also caused a concentration-dependent rise in cytosolic Ca2+, which was partially obtunded by Ca2+ deprivation. A proposed mechanism involving arachidonic acid as a negative feedback regulator of polyphosphoinositide turnover in exocrine pancreas is discussed.
Chaudhry
A
A
Department of Pharmacology, Medical College of Virginia, Richmond 23298.
Conway
B R
BR
Laychock
S G
SG
Rubin
R P
RP
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002108:Ceruletide / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D010101:Oxygen Consumption; D010179:Pancreas / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000096:biosynthesis*; D051381:Rats; D012710:Serum Albumin, Bovine / Q000494:pharmacology
D001095:Arachidonic Acids; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D012710:Serum Albumin, Bovine; D016718:Arachidonic Acid; D002108:Ceruletide; D000255:Adenosine Triphosphate; D002118:Calcium