The role of Ca2+ in regulating the catabolism of PAF-acether (1-<i>O</i>-alkyl-2-acetyl-<i>sn</i>-glycero-3-phosphocholine) in rabbit platelets

Touqui, Lhousseine; Shaw, Angus M.; Dumarey, C.; Vargaftig, B.B.

doi:10.1042/bj2410555

Cited by 18 publications

(8 citation statements)

References 28 publications

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“…6 (Blank et al, 1981;Albert and Snyder, 1983;Kramer et al, 1984). However, in addition to [3H]alkylacyl-GPC formation, there was also the formation of a neutral lipid, the synthesis of of this lipid in the mammalian endometrium (Kudolo and Harper, 1995 (Lachachi et al, 1985;Touqui et al, 1987) and by cultured rat Kupffer cells (Chao et al, 1989).…”

Section: Effect Of Calcium On Platelet-activating Factor Metabolismmentioning

confidence: 98%

Differential metabolism of exogenous platelet-activating factor by glandular epithelial and stromal cells of rabbit endometrium

Kudolo¹,

Yang²,

Chen³

et al. 1995

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Significant changes in platelet-activating factor (PAF; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine) concentration have been observed in rabbit endometrium during the preimplantation period, but, under in vitro conditions, constitutive PAF biosynthesis by isolated endometrial tissues was not easily demonstrable. Relative changes in enzymes involved in the synthesis and metabolism of PAF in the tissues may account for this disparity. In addition, during this period of preimplantation, marked changes in PAF receptor concentration have been noted. The present study examines the factors that may modulate the metabolism of exogenous [3H]PAF in the endometrium of rabbits on day 6 of pregnancy. Since preferential [3H]PAF binding in situ by the glandular epithelial, but not by the stromal, cells was demonstrated, their cell-specific metabolism of exogenous [3H]PAF was also examined. After entry into the endometrial cell, [3H]PAF was rapidly metabolized by the sequential action of cytosolic Ca(2+)-independent acetylhydrolase to [3H]lyso-PAF and this was in turn acylated by membrane-associated transacylase to [3H]alkylacyl-glycerylphosphorylcholine. PAF resynthesis was not observed and, in stromal cells, there was a significant build-up of [3H]lyso-PAF, suggesting that lyso-PAF:acetyl-CoA acetyl-transferase may be a limiting factor. In the glandular epithelial cells, however, there was a significant accumulation of a neutral lipid without a significant build-up of [3H]lyso-PAF or [3H]PAF. The neutral lipid co-migrated with the product of phospholipase C-catalysed metabolism of PAF and authentic 1-O-hexadecyl-2-acetyl-glycerol. In addition, the elution times of phospholipase C digestion of C18 PAF and the neutral lipid produced by cellular metabolism of [3H]PAF, determined by gas chromatography/flame ionization detection, were similar. It seems that it is the synthesis of the neutral lipid from reacetylated [3H]lyso-PAF that prevented [3H]PAF accumulation under in vitro conditions. This is the first documentation of the synthesis of this lipid in the mammalian uterus. The lipid may serve as the precursor for de novo PAF synthesis in the glandular epithelial cells during endometrial proliferation.

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Section: Effect Of Calcium On Platelet-activating Factor Metabolismmentioning

confidence: 98%

Differential metabolism of exogenous platelet-activating factor by glandular epithelial and stromal cells of rabbit endometrium

Kudolo¹,

Yang²,

Chen³

et al. 1995

Reproduction

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“…Divalent cations are especially important in regulating PAF metabolism. Calcium not only inhibits the acetyltransferase (75), phosphohydrolase (76), and the DTT-insensitive cholinephosphostransferase (77) in the de novo pathway of PAF biosynthesis, but it also can inhibit the deacetylation and transcylation steps in the remodeling pathway both in vivo and in v i m (103). On the other hand, calcium is essential for PAF production via the remodeling pathway (104)(105)(106).…”

Section: -Alkyl-sn-glycerol-3-p Phosphotransferase; (Iv) 1 -Alkyl-2-lmentioning

confidence: 99%

Biochemistry of Platelet-Activating Factor: A Unique Class of Biologically Active Phospholipids

Snyder¹

1989

Experimental Biology and Medicine

103

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“…On interaction with platelets, PAF is readily metabolized, 24,[105][106][107][108][109][110][111][112][113] the first process being the hy drolysis of the acetate moiety by a cytosolic acetylhydrolase. Indeed, the generation of PAF by platelets is markedly enhanced when they are treated with agents that inhibit the activity of this enzyme.…”

Section: Stimulation or Response Coupling In Plateletsmentioning

confidence: 99%

Effect of Platelet-Activating Factor on Platelets and Vascular Endothelium

Braquet¹,

Bourgain²,

Mencia‐Huerta³

1989

Semin Thromb Hemost

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Platelet-activating factor (PAF) is a phospho lipid mediator (1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphoryl choline) 1-3 named after its activity in itially described on platelets. 4 However, over the past 10 years, several other biologic activities for this mediator have been reported (reviewed by Braquet et al 5,6 ). From quantitative structure to activity re lationships, a model for the putative PAF receptor (or binding site) on platelets has been developed, 7,8 involving a hydrophobic pocket in which the alkyl chain is engaged and a recognition site for the acetyl moiety. Since 1984, several PAF antagonists ob tained from vegetable sources have been described, including kadsurenone, [9][10][11] and endogenous lignans 12 and the ginkgolide compounds (reviewed by Braquet et al 6 ). These substances have been shown to inhibit and reverse the binding of [ 3 H]-PAF to in tact platelets or membranes. In addition to the de scription of natural PAF antagonists, the knowledge of the possible structure of the recognition site for PAF on platelets has led to the development of various synthetic antagonists of the phospholipid mediator (reviewed by Braquet et al 6 ). The use of synthetic and natural PAF antagonists in diverse ex perimental and clinical models has allowed a better understanding of the role of this autacoid in throm botic and vascular diseases. The aim of the present review is to update the knowledge on the effects of PAF, especially those on platelets and vascular endothelium. MECHANISMS OF THE ACTION OF PLATELET-ACTIVATING FACTORSince platelet activation by thrombin is not in hibited by adenosine diphosphate (ADP), scaveng ing agents and cyclooxygenase blockers, a "third pathway of platelet aggregation" was postulated. [13][14][15] In 1979, Chignard et al [16][17][18][19][20][21][22] demonstrated that a sub stance identical to PAF is secreted into the supernatants of rabbit platelets stimulated with the Ca ++ ionophore A23187, thrombin, or collagen, suggest ing that PAF could be the actual mediator of the third pathway of activation. 17-21,23 PAF is also re leased by human platelets stimulated with the cal cium ionophore or thrombin, 1924 particularly when its degradation and subsequent incorporation into the platelet membrane as an acylated derivative are prevented by an acetylhydrolase inhibitor. 24 In hu mans, however, it is unclear if PAF acts as a primary aggregating agent, since PAF-induced platelet ag gregation is markedly inhibited by ADP scavengers such as creatine phosphate-creatine phosphokinase complex or apyrase. In addition, recent results show that PAF antagonists fail to interfere with thrombininduced aggregation of aspirin-treated human platelets depleted of their ADP-containing dense bodies by a snake venom component. 25 Since the dif ferences observed between rabbit and human plate lets may rely on possible alterations due to the purification procedure and the use of anticoagu lants, further studies are required to ascertain the precise contribution of PAF in the aggregation pro cess in...

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The role of Ca2+ in regulating the catabolism of PAF-acether (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) in rabbit platelets

Cited by 18 publications

References 28 publications

Differential metabolism of exogenous platelet-activating factor by glandular epithelial and stromal cells of rabbit endometrium

Differential metabolism of exogenous platelet-activating factor by glandular epithelial and stromal cells of rabbit endometrium

Biochemistry of Platelet-Activating Factor: A Unique Class of Biologically Active Phospholipids

Effect of Platelet-Activating Factor on Platelets and Vascular Endothelium

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