Synthesis of prostaglandin 6-keto F1α by cultured aortic smooth muscle cells and stimulation of its formation in a coupled system with platelet lysates

Tansik, Robert L.; Namm, Donald H.; White, Helen L.

doi:10.1016/0090-6980(78)90123-5

Cited by 68 publications

(22 citation statements)

References 10 publications

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“…Acquisition ofthis capacity correlates with the formation of a neointima of smooth muscle cells (28,29) and indicates that with time, intimal smooth muscle cells in de-endothelialized aorta synthesize and secrete increased PGI2 into the lumen. This is consistent with the finding that smooth muscle cells tested in vitro possess the capacity to synthesize PGI2 (30) and that enzymes responsible for synthesis of PGI2 are present in-all layers of the vessel wall (31). Conceivably, this increase in PGI2 production by neointimal smooth muscle cells could result either from increased enzyme activity or from increased access of substrate to smooth muscle cells.…”

Section: Discussionsupporting

confidence: 89%

Recovery of prostacyclin production by de-endothelialized rabbit aorta. Critical role of neointimal smooth muscle cells.

Eldor¹,

Falcone²,

Hajjar³

et al. 1981

J. Clin. Invest.

165

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A B S T R A C T Prostacyclin (PGI2) synthetic capacity was assayed at the surface of aortas at various intervals after removal of endothelium with a balloon catheter. Results were correlated with morphologic changes in the vessel wall seen by light microscopy, scanning and transmission electron microscopy. To assay PGI2 synthetic capacity, we applied an incubation chamber to the luminal surface of the aortas; after arachidonic acid stimulation we assayed the PGI2 synthesized with a bioassay and radioimmunoassay. PGI2 synthesis in deendothelialized aortas was determined immediately after balloon-catheter injury and at intervals of 1 h and 2, 4, 15, 35, and 70 d. PGI2 synthesis was low at 1 h and increased over time with levels at 35 and 70 d reaching that of normal artery. Scanning and transmission electron microscopy of de-endothelialized areas showed persistent absence of endothelium with formation of a neointima composed of smooth muscle cells. De-endothelialized aorta was covered with adherent platelets shortly after injury, however several days later only a few platelets adhered to the denuded surface.Results indicated that (a) endothelium is responsible for nearly all PGI2 production at the luminal surface of the normal aorta, (b) de-endothelialized muscular neointima synthesized increasing quantities of PGI2 with time after injury, and (c) increase of PGI2

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Section: Discussionsupporting

confidence: 89%

Recovery of prostacyclin production by de-endothelialized rabbit aorta. Critical role of neointimal smooth muscle cells.

Eldor¹,

Falcone²,

Hajjar³

et al. 1981

J. Clin. Invest.

165

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“…If plateletderived endoperoxides are in fact used by vasculature, then preferential synthesis of PGI2 over thromboxane would be anticipated. This hypothesis was supported by the observation that combination of lysed human platelets with lysed rat aortic smooth muscle cells increased the production of PGI2 from arachidonate, whereas platelets alone did not produce PGI2 (9). The current experiments were designed to provide direct chemical evidence regarding the ultimate fate of PGendoperoxides generated in intact platelets during aggregation or adhesion.…”

Section: Introductionmentioning

confidence: 82%

Platelet and Blood Vessel Arachidonate Metabolism and Interactions

Needleman¹,

Wyche²,

Raz³

1979

J. Clin. Invest.

179

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A B S T R A C T Exogenous arachidonate addition to intact platelets, in the absence or the presence of blood vessel microsomes, results in the production of thromboxane B2 (the stable degradation product of thromboxane A2) only. Prostaglandin (PG) endoperoxides are released from intact platelets only when thromboxane synthetase is inhibited. Thus, addition of exogenous arachidonate to imidazole-pretreated platelets in the presence of bovine aorta microsomes (source of prostacyclin synthetase) results predominantly in the synthesis of 6-keto-PGF,a (the stable degradation product of prostacyclin). Strips of intact aorta were removed from aspirin-treated rabbits, thus the isolated blood vessels were unable to convert endogenous or exogenous arachidonate to prostacyclin. Human platelets, with ['4C]arachidonate-labeled phospholipids, adhered to the blood vessel segments and released some thromboxane B2. The subsequent addition of thrombin facilitated the release of endogenous arachidonate and thromboxane, but no labeled 6-keto-PGF,, was detectable. There is therefore no direct chemical evidence of PG-endoperoxide release from human platelets during either aggregation or adhesion, which therefore precludes the possibility that blood vessels use platelet PG-endoperoxide for prostacyclin synthesis. Imidazole inhibited the thromboxane synthetase in the labeled platelets, and thereafter thrombin stimulation resulted in the release of platelet-derived, labeled PG-endoperoxides that were converted to labeled prostacyclin by the vascular prostacyclin synthetase. The latter result suggests a potential antithrombotic therapeutic benefit might be achieved using an effective thromboxane synthetase inhibitor.

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“…Vascular tissue does not synthesize TxA2 (Tansik et al, 1978). Isolated rabbit lungs did not transform PGH2 (800 ng) to any detectable TxA2 or PGI2 although both these metabolites are produced from PGH2 by microsomal preparations of rabbit lung (Sun et al, 1977).…”

Section: Discussionmentioning

confidence: 89%

“…The major metabolites produced vary between tissues. Thus platelets for example, do not contain PGI2 synthetase and transform AA predominantly to TxA2 and HETE (Samuelsson et al, 1978;Tansik, Namm & White, 1978), while many vascular beds, including the coronary circulation, metabolize AA to PGI2 but not TxA2 (Schror, Moncada, Ubatuba & Vane, 1978).…”

Section: Introductionmentioning

confidence: 99%

METABOLISM OF ARACHIDONIC ACID AND ITS ENDOPEROXIDE (PGH₂) TO MYOTROPIC PRODUCTS IN GUINEA‐PIG AND RABBIT ISOLATED LUNGS

Alabaster

1980

British J Pharmacology

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1Conversion of arachidonic acid (AA) and its endoperoxide (PGH2) to myotropic metabolites has been studied in isolated Krebs-perfused lungs of guinea-pig and rabbit. A continuous differential bioassay technique was used to measure myotropic metabolites in the lung perfusate. 2 AA was metabolized in guinea-pig lungs to thromboxane A2 (TxA2), prostacyclin (PGI2) and small amounts of a prostaglandin E2 (PGE2-like substance. The amounts of products were doserelated over the AA range used (1 to 10 ,ug). PGH2 was detected only after AA (10 ig). 3 Rabbit lungs converted AA (2.5 to 10 ig) to the same products in similar relative proportions but the amounts were 15 to 25% of those produced by guinea-pig lungs.4 Indomethacin (10 nM) preferentially inhibited metabolism of AA to prostaglandins in guinea-pig lungs but preferentially inhibited metabolism to TxA2 in rabbit lungs. Higher concentrations (50 nM) greatly reduced conversion to all the myotropic metabolites in lungs from both species.5 Imidazole (50 gM) selectively inhibited conversion of AA to TxA2 and increased conversion to PGI2 in rabbit lungs. A similar effect was produced in guinea-pig lungs but with much higher concentrations of imidazole (2.5 to 5 mM). 6 PGH2 (800 ng) was converted in guinea-pig lung to TxA2 (100 ng) and very small amounts of PGI2 (10 to 16 ng) but only unchanged PGH2 and some PGE2 were present in the lung perfusate after injection of PGH2 in rabbit lung. 7 It is concluded that guinea-pig and rabbit lung differ in their ability to metabolize AA to myotropic substances and also in their response and sensitivity to drugs which interfere with prostaglandin and TxA2 synthesis. The lungs do not appear to have an important role in converting PGH2 to PGI2.

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Synthesis of prostaglandin 6-keto F1α by cultured aortic smooth muscle cells and stimulation of its formation in a coupled system with platelet lysates

Cited by 68 publications

References 10 publications

Recovery of prostacyclin production by de-endothelialized rabbit aorta. Critical role of neointimal smooth muscle cells.

Recovery of prostacyclin production by de-endothelialized rabbit aorta. Critical role of neointimal smooth muscle cells.

Platelet and Blood Vessel Arachidonate Metabolism and Interactions

METABOLISM OF ARACHIDONIC ACID AND ITS ENDOPEROXIDE (PGH₂) TO MYOTROPIC PRODUCTS IN GUINEA‐PIG AND RABBIT ISOLATED LUNGS

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Synthesis of prostaglandin 6-keto F1α by cultured aortic smooth muscle cells and stimulation of its formation in a coupled system with platelet lysates

Cited by 68 publications

References 10 publications

Recovery of prostacyclin production by de-endothelialized rabbit aorta. Critical role of neointimal smooth muscle cells.

Recovery of prostacyclin production by de-endothelialized rabbit aorta. Critical role of neointimal smooth muscle cells.

Platelet and Blood Vessel Arachidonate Metabolism and Interactions

METABOLISM OF ARACHIDONIC ACID AND ITS ENDOPEROXIDE (PGH2) TO MYOTROPIC PRODUCTS IN GUINEA‐PIG AND RABBIT ISOLATED LUNGS

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METABOLISM OF ARACHIDONIC ACID AND ITS ENDOPEROXIDE (PGH₂) TO MYOTROPIC PRODUCTS IN GUINEA‐PIG AND RABBIT ISOLATED LUNGS