Sodium fluoride unmasks the accumulation of lysophosphatidylcholine in intact pancreatic islet cells.
When intact but dispersed neonatal islet cells, prelabelled with [14C-Me]choline, were stimulated with a calcium ionophore, ionomycin alone elicited only small rises in lysophosphatidylcholine; in contrast, pretreatment for 20 min with sodium fluoride (20mM) unmasked a consistent accumulation of lysophospholipid (to 155% of control at 1 min, 162% at 5 min and 212% at 10 min). Fluoride was shown to inhibit (by 40-50%) the reacylation of exogenous acyl- or alkyl-linked lysophosphatidylcholines by a delayed and indirect effect, whereas, in contrast, 12-O-tetradecanoylphorbol-13-acetate or dioctanoylglycerol actually augmented acylation. Thus, increased production of lysophosphatidylcholine in intact islets is obscured by rapid removal mechanisms, one of which might involve protein kinase C (or diglycerides directly). The use of sodium fluoride partially obviates this clearance, but this finding may necessitate a re-interpretation of claims that G protein agonists such as fluoride directly activate phospholipase A2 in some cells.
Metz
S A
SA
Medicine Service, Denver VA Medical Center, CO 80220.
Dunlop
M
M
D000215:Acylation; D000818:Animals; D002478:Cells, Cultured; D004789:Enzyme Activation; D005227:Fatty Acids / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000096:biosynthesis / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D051381:Rats; D012969:Sodium Fluoride / Q000494:pharmacology*
D005227:Fatty Acids; D008244:Lysophosphatidylcholines; D015759:Ionomycin; D012969:Sodium Fluoride; D010741:Phospholipases A; D054467:Phospholipases A2