Influence of Alkyl Chain Lengths in Dialkylglycerophosphocholines Towards Phospholipase A<sub>2</sub>Inhibition in Macrophages

Letourneux, Yves; Bourass, J.; Elkihel, L.; Boucrot, P; Petit, J; Welin, L.

doi:10.3109/14756369509042813

Cited by 3 publications

(2 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In previous experiments, it has been shown that incubations of cells with the substrate [3H]20:4-GPC added to the culture medium, can efficiently label membrane phospholipids of macrophages, a procedure extensively developed with either ["]or 9,23,24,32,341. The phospholipid analogue decyloctyl-GPC was efficient to inhibit 20:4 release and 20:4 cascade in macrophages.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Secreted and intracellular phospholipases A₂ inhibition by 1‐decyl 2‐octyl‐glycerophosphocholine in rat peritoneal macrophages

Boucrot¹,

Bobin‐Dubigeon

Elkihel

et al. 1998

Fundamemntal Clinical Pharma

View full text Add to dashboard Cite

Compounds able to inhibit phospholipases A2 can be considered as potential anti-inflammatory drugs. In this respect, the inhibitory effect of the phospholipid analogue 1-decyl 2-octyl-rac-glycero-3-phosphocholine (decyloctyl-GPC) added to the culture medium of rat peritoneal macrophages stimulated with ionophore A23187 was determined. (a) The substrate of phospholipase A2 1-octadecanoyl 2-[14C]eicosatetraenoyl-sn-glycero-3-phosphocholine ([14C]20:4-GPC) was added to the culture medium. In macrophages + extracellular fluids, its hydrolysis at the 2-position, produced [14C]non-phosphorous lipids which reached 12% of the dose at 0.14 microM, 73% at 0.9 and > 90% at 1.6 microM; in experiments where macrophages and extracellular fluids were analyzed separately, decyloctyl-GPC initially added at 4 microM, significantly inhibited the release of [14C]fatty acids and the eicosanoid synthesis, demonstrating its ability to inhibit secreted and/or intracellular phospholipases A2. (b) Extracellular fluids were separated from the macrophages and incubated with [14C]20:4-GPC: 48% of the dose was hydrolyzed by extracellular fluid-associated secreted phospholipase A2 and decyloctyl-GPC at 3 microM, reduced this hydrolysis by 50%. (c) [3H]arachidonic acid ([3H]20:4) was added to the culture medium and was esterified in the macrophage membrane phospholipids. Activation of intracellular phospholipase A2 induced the release of [3H] fatty acids and eicosanoid synthesis. These releases were inhibited by 50% with decyloctyl-GPC added at 4 microM. (d) [3H]20:4 and [14C]20:4-GPC were added to the culture medium of the macrophages. [3H] and [14C] fatty acids and eicosanoids were released in macrophages or extracellular fluids. They were significantly reduced by the phospholipid analogue added at 4 microM. It is concluded that secreted and intracellular phospholipases A2 were both inhibited by decyloctyl-GPC which extensively reduced the 20:4 release from exogenous and membrane phospholipids and therefore eicosanoid synthesis.

show abstract

Section: Discussionmentioning

confidence: 99%

“…All other chemicals were from Aldrich, France. The phospholipid analogue 1 -decyl 2-octyl-rac-glycero-3-phosphocholine (decyloctyl-GPC) was obtained by chemical synthesis [23]. Analytical thin layer chromatography (TLC) was performed on silica gel plates from Merck, Germany.…”

Section: Materials and Radioactive Moleculesmentioning

confidence: 99%

Secreted and intracellular phospholipases A₂ inhibition by 1‐decyl 2‐octyl‐glycerophosphocholine in rat peritoneal macrophages

Boucrot¹,

Bobin‐Dubigeon

Elkihel

et al. 1998

Fundamemntal Clinical Pharma

View full text Add to dashboard Cite

show abstract

Antileishmanial activity of rac-1-dodecy1-2-octanamido-2-deoxy-glycerophosphocholine, a new dialkylglycerophosphocholine, in vitro

Bourass

Loiseau

Bories

et al. 1996

Annals of Tropical Medicine & Parasitology

View full text Add to dashboard Cite

Uptake of the Phospholipase A₂Inhibitor 1-Dodecyl 2-[L-¹⁴q Octanamido-Sn-2-Deoxy Glycero-3-Phosphocholine by Peritoneal Macrophages

Bourass

Boucrot²,

Letourneux

et al. 1997

Journal of Enzyme Inhibition

Self Cite

View full text Add to dashboard Cite

The [14C] phospholipid analogue 1-dodecyl-2-[1-14C] octanamido-sn-2-deoxy glycero-3-phosphocholine was synthetized. With 2 short fatty chains linked by alkyl and amido bonds to positions 1 and 2 of the glycerophosphate backbone, it was an inhibitor of phospholipase A2 in ionophore A23187-stimulated macrophages. Its uptake by rat peritoneal macrophages and its resistance towards phospholipases A2 were determined at nanomolar or micromolar concentrations in the culture medium. A control substrate for phospholipases A2 activity was established with the lecithin 1-octadecanoyl 2-[3H] eicosatetraenoyl-sn-glycero-3-phosphocholine ([3H] 20:4-GPC), a source of [3H] arachidonic acid after cleavage at position 2. Non-stimulated- or ionophore A23187-stimulated macrophages incorporated extensively the [14C] phospholipid analogue added at 30-4000 nM. At 4000 nM which induced 50% inhibition of the phospholipase, 40% of the dose was found associated with the [14C] phospholipids of 2 x 10(6) stimulated macrophages after 120 min incubation, while only low amounts of [14C] non-phosphorous lipids were detected. It is concluded that the [14C] phospholipid analogue was readily taken up by the macrophages with limited hydrolysis.

show abstract

Influence of Alkyl Chain Lengths in Dialkylglycerophosphocholines Towards Phospholipase A₂Inhibition in Macrophages

Cited by 3 publications

References 41 publications

Secreted and intracellular phospholipases A₂ inhibition by 1‐decyl 2‐octyl‐glycerophosphocholine in rat peritoneal macrophages

Secreted and intracellular phospholipases A₂ inhibition by 1‐decyl 2‐octyl‐glycerophosphocholine in rat peritoneal macrophages

Antileishmanial activity of rac-1-dodecy1-2-octanamido-2-deoxy-glycerophosphocholine, a new dialkylglycerophosphocholine, in vitro

Uptake of the Phospholipase A₂Inhibitor 1-Dodecyl 2-[L-¹⁴q Octanamido-Sn-2-Deoxy Glycero-3-Phosphocholine by Peritoneal Macrophages

Contact Info

Product

Resources

About

Influence of Alkyl Chain Lengths in Dialkylglycerophosphocholines Towards Phospholipase A2Inhibition in Macrophages

Cited by 3 publications

References 41 publications

Secreted and intracellular phospholipases A2 inhibition by 1‐decyl 2‐octyl‐glycerophosphocholine in rat peritoneal macrophages

Secreted and intracellular phospholipases A2 inhibition by 1‐decyl 2‐octyl‐glycerophosphocholine in rat peritoneal macrophages

Antileishmanial activity of rac-1-dodecy1-2-octanamido-2-deoxy-glycerophosphocholine, a new dialkylglycerophosphocholine, in vitro

Uptake of the Phospholipase A2Inhibitor 1-Dodecyl 2-[L-14q Octanamido-Sn-2-Deoxy Glycero-3-Phosphocholine by Peritoneal Macrophages

Contact Info

Product

Resources

About

Influence of Alkyl Chain Lengths in Dialkylglycerophosphocholines Towards Phospholipase A₂Inhibition in Macrophages

Secreted and intracellular phospholipases A₂ inhibition by 1‐decyl 2‐octyl‐glycerophosphocholine in rat peritoneal macrophages

Secreted and intracellular phospholipases A₂ inhibition by 1‐decyl 2‐octyl‐glycerophosphocholine in rat peritoneal macrophages

Uptake of the Phospholipase A₂Inhibitor 1-Dodecyl 2-[L-¹⁴q Octanamido-Sn-2-Deoxy Glycero-3-Phosphocholine by Peritoneal Macrophages