We demonstrate that lipidomics coupled with molecular dynamics reveal unique phospholipase A2 specificity toward membrane phospholipid substrates. We discovered unexpected headgroup and acyl-chain specificity for three major human phospholipases A2. The differences between each enzyme's specificity, coupled with molecular dynamics-based structural and binding studies, revealed unique binding si...

We investigated the functional effects of epidermal growth factor (EGF) on guinea pig airways in vitro. EGF (3 ng/ml to 1 !-tg/ml) induced a concentration-dependent contraction in epithelium-denuded strips. The average of maximal contractions was 0.64±0.1 g (mean±S.E., for n=27), which was 72.0±9.5% of 100 mM KCI-induced contraction. The ECso was 12.3±1.6 ng/ml. The presence of epithelium signi...

Phospholipases A₂ (PLA₂s) represent one of the largest groups of lipid-modifying enzymes. Over the years, significant advances have been made in understanding their potential physiological and pathological functions. Depending on their calcium requirement for activation, PLA₂s are classified into calcium dependent and independent. This paper mainly focuses on brain calcium-independent PLA₂ (iPL...

In the present study, we studied the involvement of A2 phospholipases (PLA2) in alpha2-adrenergic receptor-control of preadipocyte actin cytoskeleton. For that, various PLA2 inhibitors were tested on the ability of the selective alpha2-adrenergic agonist UK14304 to induce the spreading in alpha2AF2 preadipocytes. We observed that, whereas several Ca(2+)-dependent PLA2 blockers were ineffective,...

Adenosine diphosphate (ADP) is a platelet agonist that causes platelet shape change and aggregation as well as generation of thromboxane A2, another platelet agonist, through its effects on P2Y1, P2Y12, and P2X1 receptors. It is now reported that both 2-propylthio-D-dichloromethylene adenosine 5 -triphosphate (AR-C67085), a P2Y12 receptor–selective antagonist, and adenosine-2 -phosphate-5 -phos...

Adenosine diphosphate (ADP) is a platelet agonist that causes platelet shape change and aggregation as well as generation of thromboxane A2, another platelet agonist, through its effects on P2Y1, P2Y12, and P2X1 receptors. It is now reported that both 2-propylthio-D-dichloromethylene adenosine 5 -triphosphate (AR-C67085), a P2Y12 receptor–selective antagonist, and adenosine-2 -phosphate-5 -phos...

PURPOSE The aim of this study was to demonstrate the synthesis and cellular distribution of group II phospholipase A2 and lysozyme in the main and accessory lacrimal glands. METHODS The authors studied samples of normal main lacrimal glands of seven autopsied subjects and accessory lacrimal glands of eight patients who underwent ptosis surgery. The specimens were immunostained with a rabbit a...

The hydrolysis of radiolabelled Escherichia coli phospholipids, and micellar dispersions of phosphatidylethanolamine and phosphatidylcholine, were used to characterise the phospholipase A2 activity in synovial fluid from patients with rheumatoid arthritis. Cell free fractions of synovial fluid contain a phospholipase A2 enzyme that preferentially releases [14C]oleic acid from E coli biomembrane...

Ca2+-mobilizing agonists, including hormones, neurotransmitters and growth factors, cause profound changes in cellular lipid metabolism. These changes are initiated by receptormediated activation of various phospholipases including phospholipase A2, phospholipase C and phospholipase D. Phospholipase A2 hydrolyses several phospholipids including phosphatidylinositol, phosphatidylcholine (PtdCho)...