In vivo metabolism of a new class of biologically active phospholipids: 1-alkyl-2-acetyl--glycero-3-phosphocholine, a platelet activating-hypotensive phospholipid

Blank, Merle L.; Cress, Edgar A.; Whittle, Thomas A.; Snyder, Fred

doi:10.1016/0024-3205(81)90031-x

Cited by 76 publications

(16 citation statements)

References 9 publications

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“…infusion of SNP (Sigma), an NO donor, from -10 to + 10 rnin via a syringe pump. The duration of nitroprusside infusion was limited to 10 min before and after PAF administration because the half-life of PAF is very short in plasma (12), and we reasoned that the immediate effects of PAF should be essential to subsequent production of bowel injury and, under our hypothesis, should also be antagonized by NO. The dosage of nitroprusside was titrated for each animal to normalize the MAP after L-NAME administration without causing hypotension and ranged from 2.0 to 3.0 pg/kg/min delivered in a volume of 5.7 to 8.4 pL/min.…”

mentioning

confidence: 99%

Endogenous Nitric Oxide Protects against Platelet-Activating Factor-Induced Bowel Injury in the Rat

1993

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ABSTRACT. Platelet-activating factor (PAF) causes bowel necrosis in animal models that is histologically identical to that seen in neonatal necrotizing enterocolitis, but little is known about endogenous mechanisms that might protect against PAF-induced bowel injury. We hypothesized that endogenous nitric oxide might represent such a protective mechanism. Adult male Sprague-Dawley rats were pretreated with 2.5 mg/kg NC-nitro-L-arginine methyl ester (L-NAME), a potent nitric oxide synthase inhibitor, and given injections of 1.5 pg/kg PAF 15 min later. Animals treated with normal saline placebo, L-NAME alone, and PAF alone were also studied. Superior mesenteric artery blood flow and blood pressure were continuously recorded. At the end of 2 h or upon death of the animal, hematocrit was measured and intestinal samples were taken for histologic examination and determination of myeloperoxidase activity, a measure of intestinal neutrophil content. Compared with animals given PAF alone, animals pretreated with L-NAME followed by PAF developed significantly worse bowel injury (median injury scores: 2.5 versus 0.5, p = 0.005), hemoconcentration (final hematocrit 65.2 f 2.0% versus 53.9 f 1.0%, p < 0.001), and intestinal myeloperoxidase activity (12.45 f 1.94 U/g versus 6.51 + 0.57 U/g, p < 0.01). The last two effects were further accentuated when 10 mg/kg L-NAME was given before PAF. Treatment with sodium nitroprusside, a nitric oxide donor, for 10 min before and after PAF administration reversed the effects of L-NAME. Animals pretreated with phenylephrine rather than L-NAME did not develop worse injury than animals treated with PAF alone despite comparable reductions in superior mesenteric blood flow before PAF treatment. Treatment with superoxide dismutase and catalase did not ameliorate the effects of L-NAME on PAF-induced injury, hemoconcentration, and neutrophil infiltration into the bowel. We conclude that endogenous nitric oxide defends against PAF-induced bowel injury by antagonizing certain immediate effects of PAF, particularly those leading to capillary leakage and neutrophil infiltration into the bowel. Our studies also suggest that the mechanism of action does not involve vasodilatation or scavenging of oxygen radicals. (Pediatr Res 34: 222-228,1993) Abbreviations NO, nitric oxide PAF, platelet-activating factor SOD, superoxide dismutase CAT, catalase

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confidence: 99%

Endogenous Nitric Oxide Protects against Platelet-Activating Factor-Induced Bowel Injury in the Rat

1993

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“…The effects of PAF are limited in vivo by a rapid removal of the acetyl group from the 2 position [2], This reaction is catalyzed by a PAF-specific acetylhydrolase [3] and leads to the formation of the biologically inactive 1-O-alkyl-.s'rt-glycero-3-phosphocholine (lyso-PAF).…”

Section: Introductionmentioning

confidence: 99%

The Contribution of Individual Lipoproteins to the Degradation of Platelet-Activating Factor in Human Serum

Ostermann

Kostner²,

Gries³

et al. 1989

Pathophysiol Haemos Thromb

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Platelet-activating factor (PAF) is rapidly degraded in vivo by the action of a specific acetylhydrolase. Measuring the PAF-acetylhydrolase activity in serum from 12 healthy volunteers a maximum velocity of 67.2 ± 11.8 nmol/min × ml and a K_m value of 15.8 ± 2.9 μmol/l were ascertained. More than 90% of the activity was found to be associated with lipoproteins. It was detected in isolated VLDL, LDL, Lp(a) as well as HDL₂ but not in HDL₃. The PAF-acetylhydrolase activities associated with the various lipoproteins were shown to behave like a unique enzyme with distinct kinetic properties. Because VLDL and LDL were found to take up about 5 and 2.5 times more PAF with respect to their mass than HDL, it is concluded that lipoproteins affect the PAF-acetylhydrolase activity at the level of substrate presentation. As a consequence of the distinct kinetic properties, the lipoprotein-associated PAF-acetylhydrolase activities do not contribute proportionately to the degradation of PAF in serum. The latter is shown to depend primarily on the amount of PAF-acetylhydrolase bound to the apoprotein B-containing lipoproteins.

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“…These actions of PAF are mediated mainly through speci®c cell surface receptors, although accumulation of intracellular PAF may also in¯uence cell function. PAF is degraded by the speci®c enzyme, PAF acetylhydrolase (PAF-AH) (Blank et al, 1981;Hattori et al, 1995). The physiological function of PAF-AH has not been established yet, but several hypotheses have been proposed.…”

Section: Discussionmentioning

confidence: 99%

“…PAF is a biologically active phospholipid involved in diverse physiological events such as in¯ammation and anaphylaxis (Bazan, 1995). It is inactivated by a speci®c enzyme, PAF acetylhydrolase (PAF-AH) (Blank et al, 1981), the cytosolic isoform Ib being a heterotrimer comprising a regulatory subunit of 45K, and two catalytic subunits of 30K and 29K, previously referred as a, b and g, respectively (Hattori et al, 1995). It has been shown recently that this intact PAF-AH (Ib) molecule is an unusual G-protein-like trimer (Ho et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Molecular analysis of an unstable genomic region at chromosome band 11q23 reveals a disruption of the gene encoding the α2 subunit of platelet-activating factor acetylhydrolase (Pafah1a2) in human lymphoma

et al. 1999

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In vivo metabolism of a new class of biologically active phospholipids: 1-alkyl-2-acetyl--glycero-3-phosphocholine, a platelet activating-hypotensive phospholipid

Cited by 76 publications

References 9 publications

Endogenous Nitric Oxide Protects against Platelet-Activating Factor-Induced Bowel Injury in the Rat

Endogenous Nitric Oxide Protects against Platelet-Activating Factor-Induced Bowel Injury in the Rat

The Contribution of Individual Lipoproteins to the Degradation of Platelet-Activating Factor in Human Serum

Molecular analysis of an unstable genomic region at chromosome band 11q23 reveals a disruption of the gene encoding the α2 subunit of platelet-activating factor acetylhydrolase (Pafah1a2) in human lymphoma

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