ABSTRACT
Evidence is presented that cardiolipin, a naturally occurring phospholipid, inhibits the aggregatory effect of platelet-activating factor (paf) on rabbit platelets in vitro. Bovine heart cardiolipin was shown to inhibit the aggregation of washed rabbit platelets induced by 1 x 10(-10) M and 2 x 10(-10) M paf with IC50 values (doses for half-maximal inhibition) of 8.4 +/- 0.8 x 10(-7) M and 2.6 +/- 0.6 x 10(-6) M, respectively. Phosphonocardiolipin was also able to inhibit platelet aggregation induced by 1 x 10(-10) M paf with an IC50 value of 3 +/- 1 x 10(-7) M. Both compounds, in concentrations up to 1 x 10(-5) M, were unable to aggregate washed rabbit platelets and failed to inhibit the aggregation induced by 0.9 and 1.8 microM adenosine diphosphate or 0.2-1.0 microM arachidonic acid. By contrast, the acetylated derivative of cardiolipin exerted an aggregatory effect on aspirin-treated rabbit platelets in the presence of creatine phosphate/creatine phosphokinase. This aggregation was inhibited by the specific paf antagonists BN 52021 and WEB 2086. Also, platelets treated with acetyl-cardiolipin were insensitive to the aggregatory effect of paf. Phosphatidic acid, phosphatidylglycerol, bis(dipalmitoylglycero)phosphate and their phosphono analogues were totally inactive. Similar data were obtained when platelet-rich plasma was used instead of washed rabbit platelets. Our results support the hypothesis that the effect of cardiolipin is mediated through specific paf receptors that act on the rabbit platelet membrane.
Subject(s)
Cardiolipins/pharmacology , Platelet Activating Factor/antagonists & inhibitors , Platelet Activation/drug effects , Animals , Cattle , In Vitro Techniques , Male , Molecular Structure , Phosphatidylglycerols/pharmacology , RabbitsABSTRACT
The synthesis is reported of the phosphono analogue of cardiolipin namely of 1,2-dipalmitoyloxypropyl-3-(2'-hydroxy propyl-3'-(1",2"-dipalmitoyl glycerol]biphosphonate. This was prepared by the condensation of 1,2-dipalmitoyl glycerol with 1,2-dipalmitoyl-oxypropyl-3-(2'-hydroxy propyl-3')-biphosphonate catalyzed by tri-isopropylbenzene sulfonyl chloride in pyridine. The final product was characterized by elemental analyses, phosphono phosphorus determinations, thin-layer chromatography and IR spectroscopy. The silicic acid column chromatographic behaviour of the phosphono analogue of cardiolipin was also studied.
Subject(s)
Cardiolipins/chemical synthesis , Diphosphonates/chemical synthesis , Cardiolipins/analysis , ChromatographyABSTRACT
The total phosphonolipids from human sperm have been isolated by means of preparative TLC and among these the phosphono analogue of phosphatidyl choline has been identified by chromatographic and spectral techniques.
Subject(s)
Phospholipids/isolation & purification , Spermatozoa/analysis , Chromatography, Thin Layer/methods , Humans , Male , Spectrophotometry, Infrared/methodsABSTRACT
The isolation and identification of the phosphonolipids from beef brain--right lobe, left lobe and cerebellum--is herein reported. The phosphonolipids were isolated by preparative thin layer chromatography (TLC) using the solvent system methanol/water (2:1, v/v) and identified preliminarily by TLC. The isolated phosphonolipids were subjected to silicic acid column chromatographic separation and the thus separated phosphonolipids were identified by TLC, nitrogen-phosphorus determinations and IR spectroscopy.
Subject(s)
Brain Chemistry , Phospholipids/analysis , Animals , Cattle , Chromatography, Thin Layer , Spectrophotometry, InfraredSubject(s)
Phospholipids , Animals , Chemical Phenomena , Chemistry, Physical , Phospholipids/metabolism , SphingolipidsABSTRACT
Goat spleen phosphonolipids were isolated by preparative thin-layer chromatography (TLC) using the solvent system methanol--water (2:1) and were identified by TLC, nitrogen--phosphorus determinations and IR spectroscopy. Silicic acid column chromatography of the isolated phosphonolipids confirmed the initial assignments.
Subject(s)
Phospholipids/isolation & purification , Spleen/analysis , Animals , Chromatography, Gel/methods , Chromatography, Thin Layer/methods , Goats , Silicic Acid , Spectrophotometry, Infrared/methodsABSTRACT
The total synthesis of 1-O-alkyl-2-acetyl-3-glyceryl-(2-trimethyl ammoniummethyl) phosphonate, the phosphono analogue of 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine, is described. The phosphonolipid shows much lower activity than the phospholipid stimulating serotonin release from rabbit platelets.
