Oxidative transformations of arachidonic acid in human dispersed lung cells: disparity between the utilization of endogenous and exogenous substrate

Eicosanoid release from human dispersed lung cells (HDLC) containing ca 5% mast cells was studied before and after cell activation with ionophore A23187 or anti-IgE. Basal release of eicosanoids synthesized from endogenous arachidonate was measured by radioimmunoassay. In descending order of abundance the products were: 5-hydroxyeicosatetraenoic acid (5-HETE) greater than thromboxane B2 (TXB2) greater than prostaglandin F2 alpha (PGF2 alpha) approximately immunoreactive (i)-PGE2 greater than PGD2 greater than 6-keto-PGF1 alpha approximately i-LTC4. Stimulation of HDLC with ionophore A23187 or, after passive sensitization, with anti-IgE resulted in 2-10 fold increases in the generation of individual eicosanoids. In terms of net generation the most abundant products were PGD2 and TXB2 with either stimulus. Activation with A23187 caused net release of i-LTC4 and 5-HETE, but these products were not measured after immunological activation. A more complete profile of lipoxygenase products released from HDLC dispersed from one lung was obtained after separation by high performance liquid chromatography combined with ultra violet spectroscopy and bioassay. The major products released from the cells from this lung with ionophore stimulation were 13-hydroxylinoleic acid greater than LTB4 greater than 5-HETE greater than 12-HETE greater than LTC4 greater than 15-HETE greater than 11-HETE approximately 9-HETE. When the utilization of exogenous [14C]-arachidonic acid for prostanoid biosynthesis was compared to that of endogenous unlabelled arachidonate the formation of TXB2 was consistently underestimated. These results imply compartmentalization of arachidonic acid utilization in Ca2+-activated HDLC. In unstimulated cells the proportional formation of PGD2 was overestimated when exogenous arachidonic acid was substrate. After activation with A23187 the proportions of PGD2 were similar with both substrate sources. The large proportions of PGD2 and TXB2 generated by HDLC further supports the view that these eicosanoids may be important inflammatory mediators in lung tissue.     

Comparative study of the in vitro synthesis of prostaglandins and thromboxanes in plants belonging to Liliaceae family

1. Homogenates of garlic (Allium sativum), onions (Allium cepa) and Allium porum were in vitro incubated with [14C]arachidonic acid. 2. Separation of labelled prostaglandins and thromboxanes were accomplished by thin-layer chromatography (TLC) and the Rf values were compared with those of authentic standards. 3. The prostaglandins identified were 6-keto-PGF1 alpha, PGF2 alpha, TXB2, PGE2 and PGD2. 4. PGE2 and PGD2 were the major metabolites of arachidonic acid among all the members of the Liliaceae family studied. 5. Garlic was found to have the highest capacity to metabolize the [14C]arachidonic acid into prostaglandins and thromboxanes. 6. The synthesis of prostaglandins and thromboxanes, was inhibited by preincubation of homogenates with indomethacin or was completely destroyed by boiling the plant extract prior to incubation with arachidonic acid. This confirmed the presence of cyclooxygenase in these plants.     

Total profiling by GC/NICIMS of the major cyclo-oxygenase products from antigen and leukotriene-challenged guinea-pig lung

Separation and quantitation of all the major cyclo-oxygenase products in perfused guinea-pig lungs challenged with antigen or leukotrienes C4 and D4 were achieved using a novel combined capillary column gas chromatography/negative ion chemical ionization mass spectrometric (GC/NICIMS) method. In descending order of magnitude, unchallenged lungs released thromboxane B2 (TXB2) plus its pulmonary metabolite (TXDK) greater than 6-keto-PGF1 alpha plus its 13,14-dihydro-15-keto metabolite (K2H1F1 alpha) greater than PGE2 plus PGF2 alpha greater than PGD2; after ovalbumin anaphylaxis there were increases of X 26 in TXB2 plus TXDK, X 28 in PGD2 and histamine (measured fluorometrically) but of only X 3 in 6-keto-PGF1 alpha plus K2H2F1 alpha and PGE2 plus PGF2 alpha. FPL55712 treatment greatly reduced the release of TXB2 and 6-keto-PGF1 alpha and their metabolites (showing this to be a secondary effect mediated by leukotriene action) but did not affect PGD2 output. LTC4 and LTD4 themselves induced the release of TXB2 and TXDK, as did bradykinin, but neither substance caused appreciable PGD2 release. Aside from illustrating the great value of the GC/NICIMS method for simultaneously determining all cyclooxygenase products, the main conclusions are: (i) PGD2 may be an in vitro marker for activation of lung inflammatory cells; (ii) prostacyclin and thromboxanes are actively metabolized in situ in the lung; and (iii) 'pathological subversion' of pulmonary function by anaphylaxis, leukotrienes or bradykinin principally causes thromboxane release from unknown target cells, with a smaller release of prostacyclin which may be compensatory in nature.     

Regional differences in the responses to prostanoids of circular muscle from guinea-pig isolated intestine

The effects of prostaglandins (PGs) D2, E2, F2 alpha, an epoxymethano analogue of PGH2 (U-46619), prostacyclin (PGI2), 6-keto-PGF1 alpha and thromboxane (TX) B2 were tested on spirally-cut strips of guinea-pig isolated ileum or colon. In the ileum no prostanoid exerted a marked effect on the resting tissue, but PGD2, PGE2 or PGI2 1 ug ml-1 inhibited submaximal contraction to KC1. U-46619 1 ug ml-1 either inhibited or increased contractions in KC1, but PGF2 alpha, 6-keto-PGF1 alpha or TXB2 1 ug ml-1 had no significant effect. PGE2 relaxed colonic strips whereas the other prostanoids caused contraction, except for TXB2 which had no effect. The PG antagonist SC-19220 blocked colonic contractions to the prostanoids, and the residual inhibitory effect of PGD2, U-46619 or PGI2 was demonstrated by the reduction of submaximal contractions to acetylcholine. Our results suggest that prostanoid receptors mediating inhibitory responses of circular muscle predominate in the ileum, whereas in the colon both excitatory and inhibitory prostanoid receptors occur.     

Profile of prostaglandins generated in the detrusor muscle of rat urinary bladder: effects of adenosine triphosphate and adenosine

The generation and release of PGE2, PGF2 alpha, PGD2, TXB2 and 6-keto-PGF1 alpha in the rat detrusor muscle were studied by means of radioimmunoassays. The effect of ATP (0.1 mmol/1) and adenosine (0.1 mmol/1) on the content and profile of PGs in the incubation medium was investigated. It was found that PGE2 and 6-keto-PGF1 alpha accounted for more than 80% of the total PG activity. ATP increased the amounts of PGs in the incubation medium (percentage change of the control values, N = 6: PGE2 54.53 +/- 12.69, PGF2 alpha 31.01 +/- 8.82, PGD2 44.52 +/- 12.36, TXB2 17.29 +/- 10.45, 6-keto-PGF1 alpha 36.62 +/- 5.0) but did not change their profile. Adenosine had no effect on either content or profile of the PGs. The results suggest that ATP but ot adenosine may activate PG biosynthesis via P2-purinoceptor-mediated mechanisms.     

Metabolites of arachidonic acid formed by human gastrointestinal tissues and their actions on the muscle layers.

1. Gas chromatography-mass spectrometry demonstrated the presence of arachidonic acid (AA), 6-keto-prostaglandin F1 alpha and thromboxane B2 (TxB2) in all extracts of homogenized muscle or mucosa from human stomach, terminal ileum or sigmoid colon. Prostaglandin D2 (PGD2), PGE2 or PGF2 alpha were usually found more often in the mucosal extracts. The 12-hydroxy-derivative of AA (12-HETE) was detected in all extracts of the colon but in only some of the other tissues. 2. Most prostanoids tested contracted the longitudinal muscle, the order of potency being U-46619 (an epoxymethano analogue of PGH2) greater than PGE2 greater than PGF2 alpha greater than PGD2; PGI2 usually caused relaxation, whereas its breakdown products or TxB2 had weak and variable effects. 3. U-46619 or, less potently, PGF2 alpha contracted the circular muscle, whereas PGI2 and usually PGE2 caused relaxation. PGD2, 6-keto-PGF1 alpha, 6,15-diketo-PGF1 alpha or TxB2 usually had little or no effect. 4. PGI2 antagonized contractions to some excitatory prostanoids, without greatly affecting contractions to acetylcholine. 5. For both muscle layers there was a gradient in sensitivity to prostanoids along the gastrointestinal tract. The sensitivities were stomach greater than distal ileum greater than sigmoid colon. 6. The results are discussed in relation to gastrointestinal physiology and pathophysiology.     

Relationship between arachidonic acid metabolism, myeloperoxidase activity and leukocyte infiltration in a rat model of inflammatory bowel disease

The relationship between 14C-arachidonic acid (14C-AA) metabolism, myeloperoxidase activity (MPO) and leukocyte infiltration was studied in a chronic model of inflammatory bowel disease, induced by a single intrarectal application of the hapten, trinitrobenzene sulphonic acid (TNB). The colonic damage produced by TNB was accompanied, after 12-36 hours, by a marked increase in MPO, which was directly correlated to leukocyte infiltration, assessed histologically. There was also a marked increase in the metabolism of 14C-AA, by homogenates of inflamed colon, to 12-, 15-HETE and 6-keto-PGF1 alpha as indices of lipoxygenase and cyclo-oxygenase metabolism respectively. However, a further increase in MPO-cellular infiltration, between 36-72 hours after TNB, was accompanied by a reduction in 12- and 15-HETE formation. The increase in MPO-cellular infiltration was maintained for up to 3 weeks, at which time both 12-, 15-HETE and 6-keto-PGF1 alpha formation had returned to control levels. These results suggest that these AA metabolites have a greater importance in the acute phase of the inflammatory response induced by TNB compared to the later chronic phase.     

Eicosanoid formation by mammalian intestine. Effects of some intestinal secretagogues

Intestinal tissues of man, rat, mouse, guinea-pig and rabbit were preincubated with laxatives, homogenised, and incubated with [14C]arachidonic acid. After extraction into chloroform, the eicosanoids were separated by thin layer chromatography. Metabolism of [14C]arachidonic acid into prostaglandins (PGs), and the lipoxygenase products LTB4 and 5-HETE, was stimulated by ricinoleic acid (100 micrograms/ml) or phenolphthalein (100 micrograms/ml), and to a lesser extent by picosulphate (125 micrograms/ml) and sulfosuccinate (200 micrograms/ml). Mannitol (500 micrograms/ml) had no effect. Indomethacin (1 microgram/ml) inhibited the stimulation of PG formation. The dual pathway inhibitor BW755C (1 microgram/ml) reduced the formation of prostaglandins, LTB4 and 5-HETE. In some experiments on rat colon, prostanoids were separated from lipoxygenase products, characterised by their chromatographic mobility and quantitated (relative amounts PGE2 greater than PGF2 alpha greater than TXB2 greater than PGD2). Their formation was enhanced by ricinoleic acid (100 micrograms/ml) and inhibited by either indomethacin or BW 755C (1 microgram/ml). The present results indicate that mammalian isolated gut tissue can convert [14C]arachidonic acid into both cyclo-oxygenase and lipoxygenase products, and support the suggestion that eicosanoids may participate in the laxative effect of some secretagogues.     

Formation of 6-keto prostaglandin E1 in mammalian kidneys

1 The metabolism of prostacyclin (PGI2) and 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) was studied in cell-free homogenates of rat, rabbit and guinea-pig kidney. 2 Rabbit kidney converted both PGI2 and 6-keto PGF1 alpha to a stable metabolite with chromatographic and biological activity identical to that of authentic 6-keto PGE1. Activity was found in the kidney cortex but not medulla, was inhibited by NAD+ or NADP+ (5 mM) and showed an optimum temperature requirement of 37 degrees C. 3 Guinea-pig kidney converted PGI2 but not 6-keto PGF1 alpha to a labile, biologically active metabolite which was not 6-keto pge1. 4 No conversion of prostacyclin or 6-keto PGF1 alpha to biologically active metabolites occurred in cell-free homogenates of rat kidney, liver and colon or guinea-pig liver and colon. 5 6-keto PGE1 rapidly lost spasmogenic activity on the rat stomach strip following incubation with rabbit or guinea-pig kidney supernatant in the absence of added cofactors. No loss of activity occurred on incubation with rat kidney. 6 Rutin (50 microM) potently inhibited synthesis of 6-keto PGE1 from added PGI2 by rabbit kidney cortex. This reaction was potentiated by a similar concentration of sulphasalazine, carbenoxolone, imidazole, papaverine or indomethacin. 7 The relevance of these findings for the possible physiological and pathological roles of 6-keto PGE1 in the kidney is discussed.     

The synthesis of prostaglandins and thromboxane in the mouse brain in vivo

1. The i.v. administration of convulsant doses of penetrazole or picrotoxin induced an increase in PGF2 alpha, PGE2 and TXB2-like immunoreactive material in mouse brain tissue. The onset of increase coincided with the appearance of clonic seizures. 2. The anticonvulsant drugs trimethadione and diazepam reduced both convulsions and increase of the above arachidonic acid metabolites induced by pentetrazole or picrotoxin. 3. In synaptosomal preparations of the brain, neither pentetrazole (10(-3) mol 1(-1) picrotoxin (10(-4) mol 1(-1) nor trimethadione (5 x 10(-4) mol 1(-1)) had any influence on cyclooxygenase activity as indicated by the unimpaired PGF2 alpha-synthesis. 4. Under hypoxic conditions at equal durations as the seizures, the formation of PGF2 alpha and PGE2 was less than 10% of the amount occurring after penetrazole-induced convulsions. 5. It is concluded that the seizure-induced rise of PGF2 alpha, PGE2 and TXB2 is the result of increased central nervous activity.     

Involvement of arachidonic acid metabolites in acute inflammation: detection of 6-keto-PGF1 alpha, thromboxane B2 and PGD2 in rat pleurisy induced by phorbol myristate acetate

Rat pleurisy was induced by intrapleural injection of phorbol myristate acetate (PMA), a known tumor promotor and a component of croton oil. Pleural fluids at 30 min and 1 hr after PMA-injection were collected and arachidonic acid metabolites in the fluids were measured by RIA or bioassay after fractionation through reversed phase HPLC using an ODS column. The major metabolites found in the pleural fluid were 6-keto-PGF1 alpha, TXB2 and PGD2, with a small amount of PGE2. Pretreatment with 10 mg/kg indomethacin suppressed the pleural fluid accumulation and also reduced the amount of the above metabolites to the basal levels. Treatment with OKY-046, a novel thromboxane synthetase inhibitor, reduced the level of TXB2 completely, but had no effect on those of 6-keto-PGF1 alpha and PGD2, and it had no effect on pleural fluid accumulation either. The results may indicate that PGI2 plays a role for the vascular permeability increase in the early phase of pleurisy.     

A liquid chromatography/mass spectrometric method for simultaneous analysis of arachidonic acid and its endogenous eicosanoid metabolites prostaglandins, dihydroxyeicosatrienoic acids, hydroxyeicosatetraenoic acids, and epoxyeicosatrienoic acids in rat brain tissue

A sensitive, specific, and robust liquid chromatography/mass spectrometric (LC/MS) method was developed and validated that allows simultaneous analysis of arachidonic acid (AA) and its cyclooxygenase, cytochrome P450, and lipoxygenase pathway metabolites prostaglandins (PGs), dihydroxyeicosatrienoic acids (DiHETrEs), hydroxyeicosatetraenoic acids (HETEs) and epoxyeicosatrienoic acids (EETs), including PGF(2alpha), PGE(2), PGD(2), PGJ(2), 14,15-DiHETrE, 11,12-DiHETrE, 8,9-DiHETrE, 5,6-DiHETrE, 20-HETE, 15-HETE, 12-HETE, 9-HETE, 8-HETE, 5-HETE, 14,15-EET, 11,12-EET, 8,9-EET, and 5,6-EET in rat brain tissues. Deuterium labeled PGF(2alpha)-d(4), PGD(2)-d(4), 15(S)-HETE-d(8), 14,15-EET-d(8), 11,12-EET-d(8), 8,9-EET-d(8), and AA-d(8) were used as internal standards. Solid phase extraction was used for sample preparation. A gradient LC/MS method using a C18 column and electrospray ionization source under negative ion mode was optimized for the best sensitivity and separation within 35 min. The method validation, including LC/MS instrument qualification, specificity, calibration model, accuracy, precision (without brain matrix and with brain matrix), and extraction efficiency were performed. The linear ranges of the calibration curves were 2-1000 pg for PGs, DiHETrEs, HETEs, and EETs, 10-2400 pg for PGE(2) and PGD(2), and 20-2000 ng for AA, respectively.     

Evidence against the formation of 13,14-dihydro-15-keto-prostaglandin F2 alpha following inhalation of prostaglandin D2 in man.

There is evidence that an important step in the metabolism of prostaglandin D2 (PGD2) involves 11-keto-reduction and that such a conversion might account for the reported increase in plasma concentrations of 13,14-dihydro-15-keto-PGF2 alpha in allergic asthmatic subjects challenged with inhaled allergen. Plasma concentrations of immunoreactive 13,14-dihydro-15-keto-PGF2 alpha were measured by specific radioimmunoassay both before and after inhalation of PGD2 and PGF2 alpha in 7 normal and 7 asthmatic men. In both groups of subjects, PGF2 alpha produced an approximate two fold increase in plasma concentrations of 13,14-dihydro-15-keto-PGF2 alpha that was maximal 5-7 min after inhalation. There was no significant difference in response between the normal and asthmatic subjects. In contrast, PGD2 failed to produce a change in plasma 13,14-dihydro-15-keto-PGF2 alpha concentration in either group. These results provide evidence that the conversion of PGD2 to PGF2 alpha with subsequent metabolism to 13,14-dihydro-15-keto-PGF2 alpha is unlikely to occur when PGD2 is released from mast cells in the airways.     

Antagonism by fenamates of prostaglandin action in guinea-pig and human alimentary muscle.

1 Low concentrations of meclofenamate, flufenamate or mefenamate had little effect on contractions in response to acetylcholine in any tissue studied. 2 Sodium meclofenamate potently antagonized contractions of guinea-pig ileum longitudinal muscle to prostaglandin E2 (PGE2), PGF2 alpha or PGD2. 3 In guinea-pig colonic longitudinal muscle, contractions to PGE2 were reduced by sodium meclofenamate, but contractions of the longitudinal or circular muscle to PGF2 alpha or PGD2 were less effectively inhibited. 4 In human gastrointestinal longitudinal muscle, sodium meclofenamate or flufenamate potently inhibited contractions to PGF2 alpha, but not to PGE2. 5 Sodium mefenamate or mefenamic acid, even in high concentrations, had little effect on contractions to PGF2 alpha, but tended to inhibit PGE2-induced contractions of human gastrointestinal longitudinal muscle. 6 The therapeutic advantages of prostaglandin synthesis inhibitors which also antagonize responses to certain prostaglandins are discussed.     

Modification of dyskinesias following the intrastriatal injection of prostaglandins in the rodent.

The abilities of prostaglandin E1 (PGE1), PGE2, PGD2 and PGF2 alpha to antagonize striatal dopamine function were assessed following bilateral and unilateral injections into the striata of the rat and guinea-pig. Three tests were used to assess the effects of the bilateral injections, ability to antagonize dyskinetic biting induced by 2-di-n-propylamino-5,6-dihydroxytetralin (0.025 mg kg-1 s.c.), ability to antagonize stereotyped behaviour induced by apomorphine (0.5 or 2 mg kg-1 s.c.) and ability to induce catalepsy. Asymmetry/circling behaviour revealed on challenge with apomorphine (0.25 mg kg-1 s.c.) was measured following unilateral injection into the striatum. In the rat, dyskinetic biting induced by 2-di-n-propylamino-5,6-dihydroxytetralin was antagonized by PGE1 (0.001-1 micrograms) and PGE2 (0.00001-1 micrograms) but not by PGD2 or PGF2 alpha (1 microgram). Stereotyped behaviour induced by apomorphine was not antagonized by any of the prostaglandins. A weak catalepsy was induced by PGE1 (1 microgram only), PGE2 (0.001-1 micrograms) and PGD2 (0.001-1 micrograms) but not by PGF2 alpha. Asymmetry and circling behaviour was only observed following the unilateral injection into the striatum of PGE1 and PGD2 (0.01-1 microgram) and challenge with apomorphine. In the guinea-pig the actions of PGE1 and E2 were compared with those of PGF2 alpha. Dyskinetic biting induced by 2-di-n-propylamino-5,6-dihydroxytetralin was antagonized by bilateral injections into the striatum of PGE2 (0.001-1 microgram), but not PGE1 (0.5 micrograms) and PGF2 alpha (1 microgram) but not PGE, (0.5 micrograms) and PGF2 alpha (1 microgram).(ABSTRACT TRUNCATED AT 250 WORDS)     

Facilitatory effects of selective agonists for tachykinin receptors on cholinergic neurotransmission: evidence for species differences.

1. Caffeine increased the outputs of prostaglandin F2 alpha (PGF2 alpha), PGE2 and 6-keto-PGF1 alpha from the guinea-pig uterus on days 7 and 15 of the oestrous cycle. The effect on PGE2 output depended on the age of the animals and was absent in younger guinea-pigs (< 4 months). Theophylline also stimulated the outputs of PGF2 alpha and 6-keto-PGF1 alpha, but not the output of PGE2, from the day 7 guinea-pig uterus. 2. The stimulatory effects of caffeine on the outputs of PGF2 alpha, PGE2 and 6-keto-PGF1 alpha from the guinea-pig uterus were not prevented by lack of extracellular calcium, ryanodine or ruthenium red (both inhibitors of calcium release via the ryanodine receptor), although the increase in PGF2 alpha output tended to be slower when extracellular calcium was absent. Also, ryanodine flattened and broadened the peak of increased PGF2 alpha release. 3. The calmodulin antagonists, W-7 and trifluoperazine, had no inhibitory effect on the caffeine-stimulated increases in uterine prostaglandin output. In fact, W-7 (but not trifluoperazine) greatly potentiated the action of caffeine on uterine PGF2 alpha output, but had little or no potentiating effect on the action of caffeine on uterine PGE2 and 6-keto-PGF1 alpha outputs. 4. TMB-8, an intracellular calcium antagonist, inhibited the increase in PGF2 alpha output produced by caffeine without preventing the increases in outputs of PGE2 and 6-keto-PGF1 alpha.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of the effects of different arachidonic acid metabolites on cyclic nucleotide accumulation in human peripheral lymphocytes

The effect of PGE1, PGE2, PGD2, PGF2 alpha, PGI2, PGG2, PGA1, 12L-HETE, arachidonic acid, 15- HPETEa and linolenic acid on the accumulation of cyclic AMP in human peripheral lymphocytes was studied. PGE1, PGE2 and PGD2 were essentially equipotent as stimulators of cyclic AMP accumulation (threshold at about 10(-8)M and EC50 about 0.15 microM), PGF2 alpha was about 20 times less potent, while PGG2, 12L-HETE, 15-HPETE, PGA1 and linolenic acid were inactive. PGI2 caused a weak stimulation between 5 and 600 nM and a secondary stimulation above 3 microM. Arachidonic acid had no effect on cyclic AMP levels up to 100 microM. PGE1, PGD2, PGI2 and PGF2 alpha increased cyclic GMP in the concentrations that produced a rise in cyclic AMP, but the cyclic GMP increase was of smaller magnitude. Exogenous arachidonic acid was converted mainly to 12L-HETE, HHT and thromboxane B2 by lymphocyte suspensions. This conversion could be accounted for by contamination with blood platelets. The results show that the degree of cyclic AMP accumulation in human lymphocytes following stimulation of arachidonic acid metabolism will be critically dependent upon which prostaglandins are in fact formed by cells surrounding the lymphocytes.     

阿魏酸钠对花生四烯酸代谢的影响

利用放射薄层方法测定兔血小板花生四烯酸代谢产物TXB₂,PGE₂和PGF_2α。用放射免疫法测定兔血小板TXB₂及主动脉6-keto-PGF_1α。阿魏酸钠(SF,0.1～3.2 mmol/L),抑制¹⁴C-花生四烯酸转化为TXB₂,呈剂量效应关系,IC₅₀为0.762 mmol/L。SF在较高浓度(0.8～3.2mmol/L)时亦抑制PGE₂,PGF_2α的生成。用放免法观察到,SF对血小板TXB₂和动脉壁6-keto-PGF_1α的生成均有抑制作用,对TXB₂的作用较强。结果提示,SF可抑制兔血小板和动脉壁环氧酶活性。     

Prostaglandins, thromboxanes and the pregnant rat uterus at term.

1 Prostaglandin and thromboxane release from the term pregnant (Day 22) rat uterus in vitro has been measured by radioimmunoassay and gas chromatography combined with mass spectrometry. 2 Prostacyclin (prostaglandin I2, PGI2) and thromboxane A2 (TXA2) (measured as their metabolites, 6-oxo-PGF1 alpha and TXB2, respectively) were released in large amounts, while PGE2 and PGF2 alpha were released in smaller amounts. PGD2 was released in the largest quantities. 3 Treatment of the term pregnant rat uterus in vitro with the PGI2 synthesis inhibitors, 15-hydroperoxy arachidonic acid (15-OOH AA) and tranylcypromine caused spasm of the tissue. 4 15-OOH AA caused dose-dependent increases in prostaglandin release, while tranylcypromine caused a fall in the release of PGE2 but did not affect the release of other prostaglandins. A possible reason for the effect of 15-OOH AA on prostaglandin release is discussed. 5 Indomethacin prevented spontaneous activity of the term pregnant rat uterus in vitro. Contractions were restored by prostaglandins and their order or potency was PGE2 greater than PGF2 alpha greater than PGI2 greater than PGD2 much greater than 6-oxo-PGF1 alpha = TXB2.     

乙酰丹酚酸 A──一种新型血栓素合成酶抑制剂

乙酰丹酚酸Ａ一种新型血栓素合成酶抑制剂吁文贵徐理纳（中国医学科学院、中国协和医科大学药物研究所，北京１０００５０）乙酰丹酚酸Ａ（ａｃｅｔｙｌｓａｌｖｉａｎｏｌｉｃａｃｉｄＡ，ＡＳＡＡ）有抗血小板功能作用［１］，且能明显抑制花生四烯酸（ＡＡ）代谢产物血...