Diglyceride lipase: a pathway for arachidonate release from human platelets.

Bell, Randy L.; Kennerly, Donald A.; Stanford, Nancy; Majerus, Philip W.

doi:10.1073/pnas.76.7.3238

Cited by 610 publications

(232 citation statements)

References 24 publications

Supporting

Mentioning

217

Contrasting

Unclassified

Order By: Relevance

“…However, in human polymorphonuclear cells, arachidonic acid is released (Waite et al, 1949;Walsh et al, 1981), though the synthesis of PtdCho by transmethylation is diminished (Garcia Gil et al, 1981). A similar situation has been recently reported in thrombin-stimulated platelets (Bell et al, 1978;Shattil et al, 1981). Our present data, in agreement with those of Walsh et al (1981), indicate that about 80% of the arachidonic acid generated in response to zymosan originates from PtdIns turnover.…”

Section: Specific Production Ofarachidonic Acid By Zymosansupporting

confidence: 87%

Phospholipid turnover during phagocytosis in human polymorphonuclear leucocytes

Gil

Alonso

Chiva

et al. 1982

Biochemical Journal

View full text Add to dashboard Cite

We have previously observed that the phagocytosis of zymosan particles coated with complement by human polymorphonuclear leucocytes is accompanied by a time-and dose-dependent inhibition of phosphatidylcholine synthesis by transmethylation [Garcia Gil, Alonso, Sanchez Crespo & Mato (1981) Biochem. Biophys. Res. Commun. 101, 740-7481. The present studies show that phosphatidylcholine synthesis by a cholinephosphotransferase reaction is enhanced, up to 3-fold, during phagocytosis by polymorphonuclear cells. This effect was tested by both measuring the incorporation of radioactivity into phosphatidylcholine in cells labelled with choline, and by assaying the activity of CDP-choline:diacylglycerol cholinephosphotransferase. The time course of CDP-choline:diacylglycerol cholinephosphotransferase activation by zymosan mirrors the inhibition of phospholipid methyltransferase activity previously reported. The extent of incorporation of radioactivity into phosphatidylcholine induced by various doses of zymosan correlates with the physiological response of the cells to this stimulus. This effect was specific for phosphatidylcholine, and phosphatidylethanolamine turnover was not affected by zymosan. The purpose of this enhanced phosphatidylcholine synthesis is not to provide phospholipid molecules rich in arachidonic acid. The present studies show that about 80% of the arachidonic acid generated in response to zymosan derives from phosphatidylinositol. A transient accumulation of arachidonoyldiacylglycerol has also been observed, which indicates that a phospholipase C is responsible, at least in part, for the generation of arachidonic acid. Finally, isobutylmethylxanthine and quinacrine, inhibitors of phosphatidylinositol turnover, inhibit both arachidonic acid generation and phagocytosis, indicating a function for this pathway during this process.PtdCho can be synthesized either by a cholinephosphotransferase reaction or by transmethylation. The first pathway involves the transfer of a phosphocholine group from CDP-choline to a 1,2-diacylglycerol molecule (Kennedy & Weiss, 1956). The second pathway involves the addition of three methyl groups into the amino group of a PtdEtn molecule, with S-adenosylmethionine as the methyl donor (Bremer & Greenberg, 1961). The purpose of these two pathways for PtdCho synthesis remains unclear. In rat hepatocytes cyclic AMP

show abstract

Section: Specific Production Ofarachidonic Acid By Zymosansupporting

confidence: 87%

Phospholipid turnover during phagocytosis in human polymorphonuclear leucocytes

Gil

Alonso

Chiva

et al. 1982

Biochemical Journal

View full text Add to dashboard Cite

show abstract

“…Free AA from membrane lipids is the substrate for vasodilator eicosanoid synthesis. In many tissues or cells, free AA is released by PLA 2 cleavage of the sn-2 bond of PC and PE or by PLC metabolism of PI and subsequent hydrolysis of DAG and MAG (3,5,14,15,27). In vascular tissues, both PLA 2 and PLC pathways are implicated in ACh-induced eicosanoid synthesis.…”

Section: Discussionmentioning

confidence: 99%

“…AA can be released from 2-AG by monoacylglycerol (MAG) lipase or fatty acid amidohydrolase (FAAH) (12). This PLC and DAG lipase pathway mediates AA release in human platelets (5) and bovine pulmonary artery ECs (56). Inhibition of PLC pathway by the PLC inhibitor U-73122 and the DAG lipase inhibitor RHC-80267 blocked ACh-induced vasorelaxation and AA release in porcine coronary arteries and guinea pig carotid arteries (44).…”

mentioning

confidence: 99%

Role of phospholipase C and diacylglyceride lipase pathway in arachidonic acid release and acetylcholine-induced vascular relaxation in rabbit aorta

Tang¹,

Edwards²,

Holmes³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

(ECs). In rabbit aorta, AA is metabolized through the 15-lipoxygenase pathway to form vasodilatory eicosanoids 15-hydroxy-11,12-epoxyeicosatrienoic acid (HEETA) and 11,12,15-trihydroxyeicosatrienoic acid (THETA). AA is released from phosphatidylcholine (PC) and phosphatidylethanolamine (PE) by phospholipase A 2 (PLA2), or from phosphatidylinositol (PI) by phospholipase C (PLC) pathway. The diacylglycerol (DAG) lipase can convert DAG into 2-arachidonoylglycerol from which free AA can be released by monoacylglycerol (MAG) lipase or fatty acid amidohydrolase (FAAH). We used specific inhibitors to determine the involvement of the PLC pathway in ACh-induced AA release. In rabbit aortic rings precontracted by phenylephrine, ACh induced relaxation in the presence of indomethacin and N -nitro-L-arginine (L-NNA). These relaxations were blocked by the PLC inhibitor U-73122, DAG lipase inhibitor RHC-80267, and MAG lipase/FAAH inhibitor URB-532. Cultured rabbit aortic ECs were labeled with [ 14 C]AA and stimulated with methacholine (10 Ϫ5 M). Free [ 14 C]AA was released by methacholine. Methacholine decreased the [ 14 C]AA content of PI, DAG, and MAG fractions but not PC or PE fractions. Methacholine-induced release of [ 14 C]AA was blocked by U-73122, RHC-80267, and URB-532 but not by U-73343, an inactive analog of U-73122. The data suggested that ACh activates PLC, DAG lipase, and MAG lipase pathway to release AA from membrane lipids. This pathway is important in regulating vasodilatory eicosanoid synthesis and vascular relaxation in rabbit aorta. endothelium-dependent hyperpolarizing factor; phospholipid; monoacylglycerol lipase; trihydroxyeicosatrienoic acid; hydroxyepoxyeicosatrienoic acid VASCULAR ENDOTHELIAL CELLS (ECs) regulate vascular tone by synthesis and release of many bioactive compounds. Ligands such as hormones, ACh, bradykinin, and cytokines stimulate release of arachidonic acid (AA) from cellular membranes (6,15,26,43,55), and AA induces endothelium-dependent vasodilation in isolated rabbit aorta preconstricted with phenylephrine, which is not blocked by nitric oxide (NO) synthase (NOS) and cyclooxygenase (COX) inhibitors (19,39,50). The phospholipase inhibitors mepacrine and dimethyl-eicosadienoic acid (DEDA) decrease relaxation to ACh but not AA, suggesting AA or a metabolite may be involved in the relaxations (11). AA is metabolized by COX, lipoxygenase (LO), and cytochrome P-450 pathways into bioactive eicosanoids (10,30,40,48). Using specific inhibitors in rabbit aorta, Singer and Peach (51) first concluded that a LO metabolite mediates the NO-and PG-resistant relaxation to ACh (51). The LO inhibitors cinnamyl-3,4-dihydroxy-␣-cyanocinnamate, nordihydroguaiaretic acid, and ebselen block ACh and AA-induced vasodilation in rabbit aorta (11,39,42). Previous studies in our lab identified the 15-LO metabolites of AA in rabbit aorta. AA is oxidized by 15-LO to 15-hydroperoxyeicosatetraenoic acid (15-HPETE), which is converted to hydroxyepoxyeicosatrienoic acid (HEETA) and trihydroxyeicosatrienoic acid (THET...

show abstract

“…The lower increase in arachidonic acid release than that in the lyso compound production at 1 min might be explained by the additional releasing process in the case of arachidonic acid [11]. We conclude therefore that arachidonic acid is produced mainly by the action of phospholipase A2 on phospholipids, and not by the combination of phospholipase C and acylglycerol lipases [8,9], at least under the present conditions. However, the fact that the permissive stimulation by PIA was more obvious in phospholipase A2 products (3.1-fold increase) than in phospholipase C products (1.3-fold increase) suggests that additional mechanisms are involved in the PIA stimulation of arachidonic acid release.…”

Section: Resultsmentioning

confidence: 56%

“…When phospholipase C is activated, arachidonic acid can be produced in the following two ways: (1) hydrolysis of diacylglycerol, a phospholipase C product, by lipases [8,9] and (2) degradation of phosphatidylcholine by phospholipase A2 which is stimulated by the increase in [Ca2+]1 induced by inositol trisphosphate, another phospholipase C product. In the present study, we show that Ca2+-activated phospholipase A2 participates Abbreviations used: PIA, N6-(L-2-phenylisopropyl)adenosine; TSH, thyroid-stimulating hormone (thyrotropin); PTX, pertussis toxin; CTX, cholera toxin; PMA, phorbol 12-myristate 13-acetate; RO 20-1724, 4-(3-butoxy-4-methyoxybenzyl)-2-imidazolidione; NECA, 5'-N-ethylcarboxamidoadenosine; CHA, N6-cyclohexyladenosine; CADO, 2-chloradenosine; W-5, N-(6-aminohexyl)-1-naphthalenesulphonamide hydrochloride; W-7, N-(6-aminohexyl)- in P2-purinergic agonist-induced arachidonic acid release from FRTL-5 cells.…”

Section: Introductionmentioning

confidence: 99%

Permissive stimulation of Ca(2+)-induced phospholipase A2 by an adenosine receptor agonist in a pertussis toxin-sensitive manner in FRTL-5 thyroid cells: a new ‘cross-talk’ mechanism in Ca2+ signalling.

Shimegi

Okajima

Kondo

1994

Biochemical Journal

View full text Add to dashboard Cite

We have described the pertussis toxin (PTX)-sensitive potentiation of P2-purinergic agonist-induced phospholipase C activation, Ca2+ mobilization and arachidonic acid release by an adenosine receptor agonist, N6-(L-2-phenylisopropyl)adenosine (PIA), which alone cannot influence any of these cellular activities [Okajima, Sato, Nazarea, Sho and Kondo (1989) J. Biol. Chem. 264, 13029-13037]. In the present study we have found that arachidonic acid release was associated with lysophosphatidylcholine production, and conclude that arachidonic acid is produced by phospholipase A2 in FRTL-5 thyroid cells. This led us to assume that PIA augments P2-purinergic arachidonic acid release by increasing [Ca2+]i which, in turn, activates Ca(2+)-sensitive phospholipase A2. The arachidonic acid-releasing response to PIA was, however, always considerably higher (3.1-fold increase) than the Ca2+ response (1.3-fold increase) to the adenosine derivative. In addition, arachidonic acid release induced by the [Ca2+]i increase caused by thapsigargin, an endoplasmic-reticulum Ca(2+)-ATPase inhibitor, or calcium ionophores was also potentiated by PIA without any effect on [Ca2+]i and phospholipase C activity. This action of PIA was also PTX-sensitive, but not affected by the forskolin- or cholera toxin-induced increase in the cellular cyclic AMP (cAMP), suggesting that a PTX-sensitive G-protein(s) and not cAMP mediates the PIA-induced potentiation of Ca(2+)-generated phospholipase A2 activation. Although acute phorbol ester activation of protein kinase C induced arachidonic acid release, P2-purinergic and alpha 1-adrenergic stimulation of arachidonic acid release was markedly increased by the protein kinase C down-regulation caused by the phorbol ester. This suggests a suppressive role for protein kinase C in the agonist-induced activation of arachidonic acid release. We conclude that PIA (and perhaps any of the G1-activating agonists) augments an agonist (maybe any of the Ca(2+)-mobilizing agents)-induced arachidonic acid release by activation of Ca(2+)-dependent phospholipase A2 in addition to enhancement of agonist-induced phospholipase C followed by an increase in [Ca2+]i.

show abstract

Diglyceride lipase: a pathway for arachidonate release from human platelets.

Cited by 610 publications

References 24 publications

Phospholipid turnover during phagocytosis in human polymorphonuclear leucocytes

Phospholipid turnover during phagocytosis in human polymorphonuclear leucocytes

Role of phospholipase C and diacylglyceride lipase pathway in arachidonic acid release and acetylcholine-induced vascular relaxation in rabbit aorta

Permissive stimulation of Ca(2+)-induced phospholipase A2 by an adenosine receptor agonist in a pertussis toxin-sensitive manner in FRTL-5 thyroid cells: a new ‘cross-talk’ mechanism in Ca2+ signalling.

Contact Info

Product

Resources

About