Identification of the major metabolite of prostacyclin and 6-ketoprostaglandin F1α in man

Rosenkranz, Bernd; Fischer, Christine; Reimann, I. W.; Weimer, K; Beck, G.; Frölich, Jürgen C.

doi:10.1016/0005-2760(80)90069-7

Cited by 74 publications

(54 citation statements)

References 13 publications

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“…In this part of the study both drugs were administered in the same molar dose leading to identical plasma salicylate concentrations. Prostanoid formation was assessed as platelet thromboxane synthesis as well as urinary excretion rates of PGE2, an index of intrarenal prostaglandin formation (Frolich et al, 1975), of the major metabolite of PGE, and PGE2 (PGE-M) (Hamberg & Samuelsson, 1971;Rosenkranz et al, 1983), a parameter of total body PGE formation (Hamberg & Samuelsson, 1971), and of the major metabolite of prostacyclin, 2,3-dinor-6-keto-PGF1l, (Rosenkranz et al, 1980). While acetylsalicylic acid significantly decreased urinary excretion of all measured prostanoids by about 60%, salicylate administration did not affect any of these values.…”

Section: Discussionmentioning

confidence: 99%

Effects of salicylic and acetylsalicylic acid alone and in combination on platelet aggregation and prostanoid synthesis in man.

Rosenkranz¹,

Fischer²,

Meese³

et al. 1986

Brit J Clinical Pharma

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The present study was designed to investigate the effects of salicylate on the antiplatelet action of acetylsalicylic acid as well as on in vivo prostanoid formation and platelet function in healthy volunteers. In the first study six female volunteers received 350 mg acetylsalicylic acid intravenously, with and without previous oral administration of sodium salicylate (1200 mg daily for 3 days). Urinary prostanoid excretion as well as platelet aggregation and thromboxane formation were measured before and during salicylate and after acetylsalicylic acid. In the second study seven female volunteers received sodium salicylate (52.6 mg kg‐1) or acetylsalicylic acid (60.7 mg kg‐1) for 8 days in a randomized cross‐over protocol. Urinary prostanoid excretion, platelet aggregation and thromboxane formation as well as salicylate plasma concentrations were determined before, during and after administration of each drug. Sodium salicylate did not impair the complete suppression of arachidonic acid‐induced platelet thromboxane formation and aggregation obtained by the single intravenous dose of acetylsalicylic acid in the first study. Sodium salicylate in the second study did not affect urinary excretion of prostaglandin E2, its major urinary metabolite (7 alpha‐hydroxy‐5,11‐ diketo‐tetranor‐prostane‐1,16‐dioic acid), and 2,3‐dinor‐6‐keto‐ prostaglandin F1 alpha, the main urinary metabolite of epoprostenol (prostacyclin, PGI2). In contrast, acetylsalicylic acid significantly decreased excretion rates of these prostanoids by 64, 59 and 61%, respectively. In both studies platelet aggregation and thromboxane formation induced by collagen, thrombin or arachidonic acid were not significantly affected by salicylate administration, whereas acetylsalicylic acid inhibited platelet aggregation induced by all three agents as well as thrombin‐ and arachidonic acid induced thromboxane formation.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionmentioning

confidence: 99%

Effects of salicylic and acetylsalicylic acid alone and in combination on platelet aggregation and prostanoid synthesis in man.

Rosenkranz¹,

Fischer²,

Meese³

et al. 1986

Brit J Clinical Pharma

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“…and 2,3-dinor-TXB2 (Rosenkranz et al, 1980;Roberts et al, 1981) during and after intravenous infusion of aspirin. …”

Section: Introductionmentioning

confidence: 99%

Differential effect of aspirin on thromboxane and prostaglandin biosynthesis in man.

Ritter

Cockcroft

Doktor

et al. 1989

Brit J Clinical Pharma

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1 Effects of a single intravenous dose of aspirin (600 mg) on bradykinin-stimulated prostaglandin (PG) and on thromboxane (TX) biosynthesis were determined in nine healthy male volunteers. Plasma concentrations of 6-oxo-PGF,1ll and 13,14-dihydro-15-oxo-PGF2a were measured in samples obtained during repeated 10 min intravenous infusions of bradykinin before and up to 6 h after the dose of aspirin. TXB2 was measured in serum from blood allowed to clot at 370 C. 2 Aspirin inhibited bradykinin stimulated PG and platelet TX biosynthesis 0.5 h after the dose. Serum TXB2 remained low, whereas PG synthesis recovered within 6 h. 3 Effects of intravenous sodium salicylate (600 mg) were studied identically in eight subjects. Prostanoid biosynthesis was not inhibited. 4 Biosynthesis of prostacyclin and TXA2 under basal conditions was studied in eight subjects by measuring 2,3-dinor-6-oxo-PGF1,, and 2,3-dinor-TXB2 in hourly urine samples obtained during and after intravenous infusion of aspirin and, on a separate occasion, of vehicle.5 Aspirin infusion reduced urinary excretion of both metabolites > 90%, but excretion of 2,3-dinor-6-oxo-PGF1a recovered more rapidly than did that of 2,3-dinor-TXB2. 6 We conclude that cyclo-oxygenase is rapidly synthesised in bradykinin-responsive tissues in vivo and that this reflects similarly rapid enzyme biosynthesis in tissues that produce PGI2 under basal conditions. Keywords thromboxane A2 prostacyclin prostaglandin metabolites bradykinin aspirin

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“…The urinarv metabolite selected for PG12 was 6-keto-PGF,, and that for P G E~ was PGE-M. Urinary PGE-M levels have already been successfully used to assess increased PGE production under various clinical conditions including studies in infancy (9,25,26,27). Urinary 6-keto-PGFI, levels also appear to be a reflection of systemic PG12 production as a marked increase of urinary 6-keto-PGFI, excretion has been shown during PG12 infusion in primates and humans (21,29). Furthermore, direct and indirect evidence does not identify the kidney as the major organ of urinary 6-keto-PGFI, (22,24).…”

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confidence: 99%

Urinary Excretion Rates of 6-Keto-PGF1α, in Preterm Infants Recovering from Respiratory Distress with and without Patent Ductus Arteriosus

et al. 1984

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Summaryvreterm infants have not led to conclusive results (2. 8. 15). This Patency of the ductus arteriosus in preterm infants is mediated by vasodilating prostanoids; however, reliable methods to monitor prostanoid activity or production in preterm infants are lacking. We measured the excretion rates of major and characteristic urinary metabolites of prostacyclin (PG12), PGEl, and PGE2, 6-keto-PGF1,, and 7cr-hydroxy-5,ll-diketotetranorprostane-1,16-dioic acid (PGE-M), respectively. Besides these parameters which reflect total body prostanoid turnover and production, the urinary levels of PGE2 and PGFz,, the primary prostaglandins, were measured as an index of renal prostanoid synthesis. There were four study groups. One contained 11 thriving preterm infants; a second, six preterm infants with respiratory distress syndrome (RDS); a third, 30 preterm infants with RDS and patent ductus arteriosus (PDA); and a fourth, nine fullterm infants. All infants with RDS required artificial ventilation. There were no significant differences in PGE-M, PGE2, and PGF2, excretion rates among the various groups; however, a significant increase of the 6-keto-PGF,, excretion rates was observed in the groups of infants with RDS and with and without PDA (P < 0.01 and P < 0.02, respectively). Spontaneous (n = 2) or indomethacin-induced (n = 6) closure of PDA was associated with weaning from the respirator and a concomitant drop into the normal and subnormal range of the excretion rates of 6-keto-PGF,, ( P < 0.01) and PGE-M ( P < 0.02).Abbreviations GC-MS, gas chromatography-mass spectrometry PDA, patent ductus arteriosus PG, prostaglandin PGE-M, 7cu-hydroxy-5,ll-diketotetranorprostane-l,16-dioic acid PG12, prostacyclin RDS, respiratory distress syndrome There is increasing evidence that persistent PDA in preterm infants with RDS is mediated by vasodilating prostanoids (4, 18). But it is still a matter of debate whether increased prostanoid production or increased prostanoid sensitivity of ductal tissue is the major cause of PDA persistence in preterm infants with RDS (2, 3). It is not known whether PGIz or PGE,, both vasodilating prostanoids, is the actual mediator of ductal dilation in these infants. Nor is it known which organ or tissue is mainly involved in the production of these prostanoids.Several attempts to assess prostanoid activity by radioimmunologic determinations of PGE2 in the peripheral circulation of is not unexpected due to the numerous drawbacks related to measurements of primary (parent) PGs (1 1). There are four major concerns of this approach. 1) Very low circulating levels of primary PGs are expected because of the very rapid metabolism of these compounds and single blood measurements might easily miss rapid fluctuation of PG release. 2) Primary PGs might be released from platelets and white cells during collection and handling of blood samples. 3) Protein binding of prostanoid in blood and plasma may interfere with several conventional extraction procedures. 4) Radioimmunologic assays of prostanoids may lack the...

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Identification of the major metabolite of prostacyclin and 6-ketoprostaglandin F1α in man

Cited by 74 publications

References 13 publications

Effects of salicylic and acetylsalicylic acid alone and in combination on platelet aggregation and prostanoid synthesis in man.

Effects of salicylic and acetylsalicylic acid alone and in combination on platelet aggregation and prostanoid synthesis in man.

Differential effect of aspirin on thromboxane and prostaglandin biosynthesis in man.

Urinary Excretion Rates of 6-Keto-PGF1α, in Preterm Infants Recovering from Respiratory Distress with and without Patent Ductus Arteriosus

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