Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: CAS:22276-27-3 (hexadecyl)
 2,701 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1-0-Hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (1-hexadecyl-2-acetyl-GPC, platelet activating factor, PAF) was previously shown to produce profound hypotension and sympathetic activation in conscious rats. To determine the role of the sympatho-adrenomedullary system in the cardiovascular responses elicited by 1-hexadecyl-2-acetyl-GPC, the vasoactive phospholipid was administered (1 nmol per 300 g) to a) intact, b) bilaterally demedullated, and c) propranolol- (a beta-adrenoceptor blocker) treated SHR and WKY rats. The hypotensive response to 1-hexadecyl-2-acetyl-GPC was prolonged in demedullated or propranolol-pretreated WKY rats and in propranolol-treated SHR rats. The extreme tachycardia produced by 1-hexadecyl-2-acetyl-GPC in both the WKY and SHR rats was abolished by propranolol pretreatment. Pressor responses to norepinephrine during the 1-hexadecyl-2-acetyl-GPC-induced hypotension in propranolol-pretreated rats were suppressed in both the normotensive and SHR rats. Plasma acetylhydrolase activity, which inactivates PAF, was higher in hypertensive (SHR) rats or demedullated WKY rats than in the normotensive (WKY) rats. These results show that the tachycardia evoked by 1-hexadecyl-2-acetyl-GPC is mediated solely by sympathetic activation and the beta-adrenergic receptors and further indicate the major role of the sympathetic system and beta-adrenoceptors in recuperation from 1-hexadecyl-2-acetyl-GPC-induced shock. The data also suggest that acetylhydrolase in serum is an important regulatory enzyme for controlling PAF levels in the vascular compartment.
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PMID:The adrenergic system and the cardiovascular effects of platelet activating factor (1-0-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine) in SHR and WKY rats. 299 12

Human polymorphonuclear neutrophils rapidly incorporated radiolabeled platelet-activating factor, 1-O-[hexadecyl-9, 10-3H2]-2-acetyl-sn-glycero-3-phosphocholine ([3H]PAF), and then metabolized it into its sn-2-fatty acyl derivative. Fractionation of radiolabel-pretreated cells over Percoll gradients revealed that virtually all of the intact [3H]PAF was located in nongranule membranes that were enriched with alkaline phosphatase and cell surface glycoproteins. While still membrane associated, the ligand was rapidly converted to its acyl derivative and then more slowly transferred to specific granules and, to a lesser extent, azurophilic granules. In contrast, neutrophils did not metabolize [3H]PAF at 4 degrees C but rather gradually accumulated it in their alkaline phosphatase-enriched membrane subfractions. These same subfractions contained receptors for the ligand, as determined by their capacity to bind [3H]PAF specifically. Binding was readily saturated, partially reversible, and fit a two receptor model; dissociation constant (Kd) values for high and low affinity sites were 0.2 and 500 nM, respectively. Receptors with similar affinities were detected in whole cells. Furthermore, the potencies of several structural analogues in inhibiting binding of [3H]PAF to membranes correlated closely with their respective potencies in stimulating degranulation responses. Finally, quantitative studies suggested all or most of the cell's receptors were membrane associated. We conclude that PAF rapidly enters cellular membranes to bind with specific receptors that trigger function. The intramembranous ligand is also deacetylated, acylated, and then transferred to granules. This metabolism may be sufficiently rapid to limit ligand-receptor binding and distort quantitative analyses of receptors.
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PMID:Binding and metabolism of platelet-activating factor by human neutrophils. 301 27

A Ca2+-dependent lysophospholipase D activity in microsomal preparations from the rabbit kidney medulla hydrolyzes the choline moiety from 1-O-[9,10-3H]hexadecyl-2-lyso-sn-glycero-3-phosphocholine (lyso-PAF) to form 1-O-[9,10-3H]hexadecyl-2-lyso-sn-glycero-3-P; the latter is subsequently dephosphorylated by a phosphohydrolase to 1-O-[9,10-3H]hexadecyl-sn-glycerol. Sodium vanadate, which is known to inhibit phosphohydrolases, reduces the proportion of hexadecylglycerol and increases the formation of hexadecyl-lysoglycerophosphate. Essentially no hydrolysis occurs when the sn-2 position of the hexadecyllysoGPC substrate contains an acyl moiety. The lysophospholipase D in rabbit kidney is of microsomal origin and has a broad pH optimum between 8.0 and 8.8, with the activity decreasing sharply from pH 7.6 to 7.2. Wykle et al. (Biochim. Biophys. Acta 619 (1980) 58-67) have previously demonstrated the existence of a microsomal lysophospholipase D (specific for ether lipid substrates) in rat tissues that requires Mg2+ and exhibits a pH optimum of 7.2; high activities of the Mg2+-dependent lysophospholipase D were found in liver and brain, but not in kidney. In contrast to the Mg2+-dependent lysophospholipase D in rat tissues, the renal enzyme from rabbits requires Ca2+ (5 mM), whereas Mg2+ (5 mM) exhibits little stimulatory action. Under optimal assay conditions (0.1 M Tris-HCl (pH 8.4)/5 mM CaCl2), lysophospholipase D in the rabbit kidney medulla has an activity of 2.7 nmol/min per mg protein compared to 0.9 nmol/min per mg protein for the lysophospholipase D in the rat kidney medulla (0.1 M Tris-HCl (pH 7.2)/5 mM MgCl2). The Ca2+-dependent lysophospholipase D is highest in the liver and kidney medulla from rabbits, but is very low in rat tissues; similar activities were found in male and female rabbits. Our data indicate that the divalent metal ion requirements for expression of maximum lysophospholipase D activities can differ markedly among animal species and also suggest the microsomal Ca2+-dependent lysophospholipase D is an important catabolic route for lyso-PAF metabolism in rabbit renomedullary tissue.
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PMID:The metabolism of lyso-platelet-activating factor (1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine) by a calcium-dependent lysophospholipase D in rabbit kidney medulla. 303 38

Platelet-activating factor (PAF; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) results in contraction of isolated glomeruli and cultured mesangial cells and concomitantly causes release of arachidonic acid and prostaglandin E2 (PGE2) formation. The kidney and isolated glomeruli can also generate material that has PAF bioactivity. We therefore examined the capacity of isolated renal glomeruli and cultured glomerular mesangial cells from rats to form PAF. Both isolated glomeruli and cultured mesangial cells transformed 1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine ([3H]lyso-PAF) into a labeled product comigrating both on thin-layer chromatography (TLC) and high-pressure liquid chromatography (HPLC) with authentic PAF. Using rabbit platelet aggregation as bioassay for PAF, we found that isolated glomeruli produced 4 +/- 2 pmol/mg glomerular protein of PAF-like material, and mesangial cells produced 30 +/- 8 pmol/mg cell protein when stimulated with A23187 (10(-5) M) for 30 min. The major species of the PAF material produced by mesangial cells was identified as 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine after HPLC separation, followed by fast atom bombardment and gas chromatography-mass spectrometry. These results show that glomerular mesangial cells can produce PAF, which could contribute locally to the regulation of glomerular function.
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PMID:Production of platelet-activating factor in glomeruli and cultured glomerular mesangial cells. 308 18

Two physicochemical methods have been developed for the quantitative analysis of lyso-platelet activating factor (lyso-PAF) based on gas-liquid chromatography-mass spectrometry (GLC/MS) and fast atom bombardment-mass spectrometry (FAB/MS) using stable isotope dilution. After addition of deuterated internal standards, lyso-PAF produced from neutrophils was purified by silicic acid chromatography and thin-layer chromatography (TLC). The GLC/MS assay employed phospholipase C or hydrofluoric acid for hydrolysis of the phosphocholine moiety to yield ether monoglycerides. Condensation of monoglycerides with acetone yielded the 1-O-alkyl-2,3-isopropylidene glycerol which could be analyzed by GLC/MS. The ions corresponding to M-15 fragments for both the labeled and unlabeled derivatives were monitored in a selected ion recording mode. Standard curves were found to be linear over the range tested (10-2000 ng) with a limit of detection found to be below 200 pg injected on column. For the FAB/MS assay, the unmodified lyso-PAF was well suited for direct analysis; however, the limit of detection (S/N greater than 3) using a glycerol matrix was found to be 5 ng placed on the probe tip. It was found that human neutrophils contain approximately 300 pg/10(6) cells which increased 2-3-fold during the 5-min period following challenge with 1.9 microM calcium ionophore, A23187. Two molecular species of lyso-PAF were identified as hexadecyl and octadecyl ethers at sn-1 with the octadecyl molecular species of lyso-PAF predominating in abundance after stimulation.
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PMID:Quantitation of lyso-platelet activating factor molecular species from human neutrophils by mass spectrometry. 310 21

The present study showed that platelet-activating factor (1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine, PAF), but not lysoPAF (1-O-hexadecyl-sn-glycero-3-phosphocholine) rapidly (within 15 sec) stimulated the incorporation of both [1-14C]arachidonate and [1-14C]docosahexaenoate into phosphatidylinositol (PI) and phosphatidylcholine (PC) in human neutrophils. Concomitantly, it inhibited the formation of labeled phosphatidic acid from both fatty acids. The magnitude of stimulation (percentage of control) was greater in PI than in PC for the incorporation of arachidonate and vice versa for the incorporation of docosahexaenoate. It reached a maximum at 10(-7) M and started to decline at 10(-6) M. Extracellular Ca2+ was not essential for the action of PAF on phospholipid acylation. The distribution of labeled arachidonate in the molecular species of PC was not altered by PAF after 1 min incubation, suggesting that the increased formation of arachidonyl-PC during the early stage of neutrophil-PAF interaction was not originated from the added PAF. No measurable changes in the mass of each phospholipid were detected in neutrophils challenged by PAF from 15 sec to 2 min. The data suggest that the increased incorporation of extracellular fatty acids into PI and PC elicited by PAF may be secondary to increased deacylation of these phospholipids, and the magnitude of stimulation reflects the specificity of acyltransferase catalyzing the acylation of lysoPI and lysoPC by fatty acyl-CoA.
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PMID:Platelet-activating factor modulates phospholipid acylation in human neutrophils. 311 May 33

PAF and structural analogues were investigated for their in vivo effects on fibrinolytic activity (FA) in the rat. The i.v. administration of 1 and 4 micrograms/kg PAF caused a dose-dependent increase in FA which was shown to be attributable to the release of tissue-type plasminogen activator (t-PA). 1-O-hexadecyl-2-O-ethyl-glycero-3-phosphoric acid-2'-N-propargyl-N,N'- dimethylammoniumethyl ester (I) and 1-O-hexadecyl-2-(n-propyl)-propanediol-3-phosphocholine (II) increased FA according to their proaggregatory activity. In contrast, 1-O-hexadecyl-2-O-ethyl-rac-glycero-3-phosphoric acid-5'-trimethylammoniumpentyl ester (III), a competitive antagonist of PAF, reduced the PAF induced increase of FA by 30%. Under identical conditions BN 52021 given at 1 and 10 micrograms/kg amounts diminished the effect of PAF by 47 and 77%, respectively. These results indicate that the PAF induced PA release in vivo is receptor mediated.
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PMID:Effects of synthetic analogues of platelet-activating factor (PAF) on fibrinolytic activity in the rat. 315 Feb 68

1-O-hexadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine (platelet activating factor, PAF), (1.9 mumol) was prepared from the total lipid extract of the protozoan Tetrahymena pyriformis 9 x 10(7) cells. The procedure involved mild alkaline hydrolysis of the total lipids, followed by acetylation and purification of the product by preparative TLC and HPLC. The yield was 60% with respect to the content of 1-O-alkyl-2-acyl-sn-glyceryl-3-phosphorylcholine in the total lipids, determined after preparative TLC. The alkyl side chain of the semisynthetic PAF was composed of hexadecyl residue. Our product was identified as PAF according to its biological activity, the chromatographic behaviour on TLC and HPLC, the physicochemical properties and the behaviour under treatment with PLA2 and Lipase from Rhizopus arrhizus. The above procedure is proposed as a facile, inexpensive and convenient method.
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PMID:Semisynthetic preparation of 1-O-hexadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine (platelet activating factor). 324 64

Acetylhydrolase, the enzyme which inactivates platelet-activating factor (PAF, 1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholine), was selectively released from bovine platelets by aggregation with physiological concentrations (0.1-10 nM) of PAF with no cell lysis. The release of the acetylhydrolase paralleled that of serotonin. The acetylhydrolase released was active over a broad pH range (pH 5.4-8.6) and was not affected by Ca2+ (1-4 mM) or EDTA (1-8 mM). The Km value of the enzyme was 4.6 microM. Net specific acetylhydrolase activity recovered in the 130,000 x g supernatant after stimulation with PAF could be determined in the presence of EDTA without the activity of Ca2+-dependent phospholipase A2 which was also released from the cells at the same concentration of PAF. The acetylhydrolase was inhibited competitively by specific PAF antagonists, rac-3-(N-n-octadecylcarbamoyloxy)-2-methyoxypropyl-2-thiazolioe thyl phosphate (CV-3988) and (2RS)-1-O-hexadecyl-2-O-ethyl-3-O-(7-thiazolinoheptyl)-glycerol methanesulfonate (ONO-6040). Their Ki values for the enzyme were 1.17 microM and 0.84 microM, respectively. The release of the enzyme could also be detected when the platelets were aggregated with ADP (2.3 microM) or thrombin (0.5 unit). These results suggest that the enzyme released from the aggregated platelets to the blood plasma may also have a physiological function cooperating with the plasma acetylhydrolase.
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PMID:Release of acetylhydrolase from platelets on aggregation with platelet-activating factor. 334 57

A gas chromatographic method with a glass capillary column and electron-capture detection is proposed for the characterization and quantification of 1-O-hexadecyl-2-O-acetyl-sn-glycero-3-phosphocholine (PAF C16) using the corresponding 1-O-hexadecyl-2-O-acetyl-sn-glycero-3-heptafluorobutyrate derivative and, as an internal standard, 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine. The reproducibility was approximately 5% and amounts as low as 20 pg could be measured. The method was specific and allowed the quantification of PAF C16 in supernatants from stimulated human polymorphonuclear neutrophils.
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PMID:Characterization and quantification of PAF-acether (platelet-activating factor) as a heptafluorobutyrate derivative of 1-O-alkyl-2-acetyl-sn-glycerol by capillary column gas chromatography with electron-capture detection. 344 54


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