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1.
A rabbit lung preparation, perfused , was used to examine pulmonary metabolism of prostaglandin A1 (PGA1) and to compare the vasoconstrictor actions of PGA1, prostaglandin F2α (PGF2α) and angiotensin II. PGF2α caused significantly more, and angiotensin II significantly less, vasoconstriction than did an equimolar concentration of PGA1. Of three likely PGA1 metabolites only 15-keto-PGA1 had any significant vasoconstrictor action. Furosemide and aminophylline (10?3 M) reduced PGA1, PGF2α or angiotensin II-induced vasoconstruction. Diphloretin phosphate potentiated the vascular effect of angiotensin II. Furosemide (10?3 M) and DPP (9.5 × 10?6 M) significantly reduced pulmonary metabolism of PGA1 while aminophylline (10?3 M) had no effect on this process. Perfusion of the lungs with a hypoxic medium had no effect on PGA1 metabolism. 相似文献
2.
We have recently reported that cartilage has two sites for prostaglandin (PG) action. One site (S1) is stimulated by PGA1, PGE1 and PGF1α and elevates tissue cyclic 3′5′adenosine monophosphate (cAMP). A second site (S2) is activated by PGA1 (but not PGE1 or PGF1α) and inhibits the synthesis of cartilage macromolecules. The present study is an investigation of the effects of PGB1 on embryonic chicken cartilage chondromucoprotein synthesis in vitro. PGB1 was found to inhibit chondromucoprotein synthesis with an apparent affinity for S2 which was similar to that of PGA1. The maximal inhibition produced by PGB1 was, however, approximately one-half the maximal inhibition caused by PGA1. Studies of the combined effects of PGB1 and PGA1 were consistent with the hypothesis that both classes of prostaglandins act at a common site (S2) with about equal affinity but that PGB1 has a lower intrinsic activity than PGA1. Similar studies of the combined effects of PGE1 or PGF1α with PGA1 indicate that neither PGE1 nor PGF1α binds significantly to S2. An independent effect of PGB1 to activate S1 and elevate tissue cAMP was also found. 相似文献
3.
Shizuko Takano Akira Sawano Hiroshi Watanabe Takehiko Suzuki 《Prostaglandins & other lipid mediators》1978,15(3):485-489
Effects of prostaglandins (PG) E1, E2, F2α, A1, A2 nad B2 were studied on guinea-pig isolated tracheal chains. PGF2α, B2 and A2 produced contraction, PGE1 and E2 relaxation of the chain, but A1 produced no response. 1) From the cumulative dose response curves, PGF2α was more active in producing concentration than B2 or A2, though its effect was less than that of acetylcholine (ACh). PGE1-induced relaxation was less than the response to isoproterenol. 2) PGE1 and E2 1 μg/ml caused a 26.1 ± 3.83% (n=5) or a 9.5 ± 3.36 (n=6) decrease of ACh (1 μg/ml)-induced contraction respectively. The degree of relaxation produced by E1 was greater than that by E2 (P<0.01). 3) After five minutes preincubation with each of PGA1, A2, B2 and F2α in concentrations which did not produce any effect, ACh-induced contraction was augmented only after PGA2 (P<0.05). 相似文献
4.
C.John Harris Norman Whittaker Gerald A. Higgs J.Michael Armstrong Paula M. Reed 《Prostaglandins & other lipid mediators》1978,16(5):773-787
12-Aza-prostaglandin (PG) analogues containing the pyrrolidine-2,4-dione ring system have been synthesized from
,2-disubstituted glycine esters via cyclisation of their
-ethoxycarbonylacetyl derivatives. 5-(6-Carboxyhexyl)-1-octylpyrrolidine-2,4-dione (5) had little or no PG-like activity on superfused intestinal or vascular smooth muscle preparations but it selectively antagonised smooth muscle responses to PGE2, PGE1, PGF2α and PGA2in vitro. At a concentration of 10−5 g/ml it reduced responses of the rat stomach strip to PGE2 by over 80% but did not affect responses of this tissue to acetylcholine, 5-hydroxytryptamine (5-HT) or bradykinin. Polyphloretin phosphate (PPP), the known PG antagonist, had a similar effect at the same concentration (10−5 g/ml).5-(6-Carboxyhexyl)-1-(3-hydroxyoctyl)pyrrolidine-2,4-dione (12) had the same profile of activity on superfused smooth muscle preparations as PGE2 or PGA2. On intravenous injection into anaesthetised rats it caused dose-dependent falls in arterial blood pressure with associated tachycardias, which is typical of the response to PGE2. The smooth muscle activity of (12) was not reduced by passage through isolated perfused guinea-pig lungs nor was its potency as a vasodepressor increased when given intra-arterially to rats. These results suggest that, unlike PGE2, this analogue is not removed by the pulmonary circulation. 相似文献
5.
Hollis J. Hawkins Alan G.E. Wilson Marshall W. Anderson Thomas E. Eling 《Prostaglandins & other lipid mediators》1977,14(2):251-259
We have investigated the uptake and subsequent metabolism of the prostaglandins (PGs) PGE1, PGA1, and PGB1 by rat, guinea pig and rabbit isolated perfused lungs (IPL). Significant species differences were not observed in the uptake or metabolism of any PG on passage through the IPL. However, differences in the uptake of PGA1 and PGB1 and in the metabolism of PGA1 were observed with a given species when the composition of the perfusion medium was varied. The IPL removed minimal amounts (<20% of the supply rate) of PGA1 and PGB1 from the circulation when the perfusate contained 4.5% bovine serum albumin (BSA). In the absence of BSA, however, both PGA1 and PGB1 were substantially removed from circulation (~53% of the supply rate) and PGA1 was also metabolized. The composition of the perfusate had no effect on the uptake and metabolism of PGE1 which was always taken up and metabolized to a greater extent than was PGA1 and PGB1. Thus, the apparent species differences previously reported for the pulmonary biotransformation of PGA can result from differences in the perfusion medium used. Our data suggest that both plasma protein binding and a transport system play important roles in determining the selectivity of the uptake of PGs by the lung. 相似文献
6.
J. Mnnist H. Toivonen J. Hartiala Y.S. Bakhle P. Uotila 《Prostaglandins & other lipid mediators》1981,22(2):195-204
The effects of cigarette smoke on the metabolism of exogenous arachidonic acid (AA) were investigated in isolated hamster lungs. Arachidonate was injected into the pulmonary circulation and the metabolites were analysed from the nonrecirculating perfusion effluent by thin layer chromatography. After the pulmonary injection of 66 nmol of 14C-AA about 20 % of the injected radioactivity appreated in the perfusion effluent mostly as metabolites in six minutes. When isolated lungs were ventilated with cigarette smoke during the perfusion, the amounts of PGF2α, PGE2 and two unidentified metabolite groups increased in the lung effluent. In two other experimental series hamsters were exposed to cigarette smoke before the lung perfusion either once for 30 min or during one hour daily for ten consecutive days. Neither pre-exposures caused any changes in the amounts of arachidonate metabolites in the lung effluent. 相似文献
7.
The inotropic and chronotropic actions of prostaglandin (PG) types PGE1, PGA1, and PGF2α were studied in isolated guinea pig right and left atria, and papillary muscles; rabbit atria; and toad ventricular strips in order to more completely define the cardiac contractile properties of PG. All three prostaglandins, in muscle bath concentrations of 10μg/ml, exerted positive inotropic and chronotropic actions on guinea pig atrium. These contractile effects were persistent after removal of PG from the muscle bath and appeared to limit the relative response to a subsequent dose of PG. The inotropic action of PGE1 was present over a wide range of bath calcium concentrations (1.1 to 4.4 mM/L). Beta adrenergic receptor blockade, histamine blockade, and pretreatment with reserpine failed to significantly affect the inotropic actions of PG. Norepinephrine and histamine produced more potent inotropic and chronotropic effects on guinea pig atria than did PG and these contractile effects did not exhibit persistence or tachyphylaxis. The prostaglandins did not significantly affect dose response curves for norepinephrine inotropic and chronotropic actions. The prostaglandins had no effect on the force or frequency of contraction in rabbit atria. PGE1 exerted a positive inotropic effect on toad ventricular myocardium whereas PGA1 had no effect and PGF2α had a negative inotropic action. 相似文献
8.
George S. Eisenbarth David K. Wellman Harold E. Lebovitz 《Biochemical and biophysical research communications》1974,60(4):1302-1308
The effects of various prostaglandins (PG) on the in vitro synthesis of macromolecules by two transplantable chondrosarcomas were studied. Prostaglandin A1 markedly inhibited the incorporation of radioactive precursors into chondromucoprotein, total protein, RNA and DNA of both a well differentiated rat chondrosarcoma and a poorly differentiated murine chondrosarcoma. PGE1 and PGF1α had no effects on the synthesis of macromolecules by either tumor. PGA1 inhibitory effects occurred over a dose range of 1 to 25 μg/ml. PGA1 had no effect on the synthesis of macromolecules by liver. The data indicate that malignant transformation of cartilage cells does not alter their responsiveness to PGA1. 相似文献
9.
John W. Greiner Robert E. Kramer Howard D. Colby 《Prostaglandins & other lipid mediators》1979,17(4):587-597
Studies were carried out to investigate the effects of prostaglandins (PG) on adrenal microsomal steroid and drug metabolism in the guinea pig. The addition of PGE1, PGE2, PGA1, PGF1α or PGF2α to isolated adrenal microsomes produced typical type I difference spectra. The sizes of the spectra (ΔA385–420) produced by prostaglandins were smaller than those produced by various steroids including progesterone, 17-hydroxyprogesterone and 11β-hydroxyprogesterone. However, the affinities of prostaglandins and steroids for adrenal microsomal cytochrome P-450, as estimated by the spectral dissociation constants, were similar. Prior addition of prostaglandins to isolated adrenal microsomes did not affect steroid binding to cytochrome P-450 or the rate of steroid 21-hydroxylation. In contrast, prostaglandins inhibited adrenal metabolism of ethylmorphine and diminished the magnitude of the ethylmorphine-induced spectral change in adrenal microsomes. The results indicate that prostaglandins inhibit adrenal drug metabolism by interfering with substrate binding to cytochrome P-450. Since 21-hydroxylation was unaffected by PG, different cytochrome P-450 moieties are probably involved in adrenal drug and steroid metabolism. 相似文献
10.
Shizuko Takano Shigeru Itagaki Kunio Sakurai Takehiko Suzuki 《Prostaglandins & other lipid mediators》1980,20(3):579-586
Influences of prostaglandin(PG)s on electrophoretic mobilities and aggregation of rabbit platelets were studied. The PGs studied (PGI2, PGE1, PGD2, PGE2, PGF2α, PGA2 and PGA1) had no effect on platelet electrophoretic mobility. However, both PGE1 and PGI2 in 0.3 and 3.0 μM inhibited ADP-induced aggregation and ADP-induced decrease in the mobility. PGD2 in 0.3 and 3.0, and PGE2 in 30 μM inhibited the aggregation but did not depress the ADP-induced decrease in the mobility. PGF2α, PGA2 and PGA1 had no effect on the decrease in electrophoretic mobility and on the aggregation caused by ADP. 相似文献
11.
《Animal reproduction science》1987,14(2):103-113
Six cyclic Holstein dairy cows were anesthetized on days 12–14 post-oestrus. Reproductive tract was exposed by midventral incision, and the ovarian (utero-ovarian) vein and facial artery cannulated. Oviduct was ligated, and a catheter (affluent) introduced into the tip of the uterine horn. The uterine horn was ligated above the uterine body, a second catheter (effluent) introduced into the uterine lumen, and an electromagnetic blood flow transducer placed around the uterine artery. On the day following surgery, the uterine horn was infused constantly for 9 h with PGF2α dissolved in PBS (0.7 ml/min, 177 ng/ml). During periods 1 and 3 (first 3 h and last 3 h, respectively) only PGF2α was perfused; during period 2 (between 3 h and 6 h) 101tgμg/ml of PGE2 were added to the perfusate together with PGF2α. Uterine venous and peripheral blood samples were collected simultaneously every 15 min, and uterine blood flow recorded continuously. Least-square means for PGF measured in uterine venous drainage for periods 1, 2 and 3 were 315 ± 26, 557 ± 24 and 511 ± 26 pg/ml, respectively (P < 0.05). Uterine blood flow values were 52 ± 5, 67 ± 4 and 61 ± 4 ml/min for periods 1, 2 and 3 (P < 0.08), respectively.Results do not support the hypothesis that the antiluteolytic effect of PGE2 is associated with a suppression of uterine PGF2α release into the circulation. Greater release of PGF to the circulation in period 2 (addition of PGE2) is probably the result of the vasodilatory effect of PGE2 on uterine endometrial vasculature. 相似文献
12.
The developmental pattern of fetal and neonatal rabbit lungs to metabolize arachidonic acid (AA) to different cyclo-oxygenase products was studied in isolated rabbit lungs, which were perfused with Krebs bicarbonate buffer. 14C-AA (66 nmol) was injected into the pulmonary circulation and the nonrecirculating perfusion effluent was collected for four minutes. About ten per cent of the injected radioactivity was found in the 0–4 min perfusion effluent. The metabolites of AA in the effluent were analyzed by thin layer chromatography. The major metabolites of AA were PGE2 and its 15-keto-derivates, but also PGF2α and its 15-keto-derivates, TXB2 and 6-keto-PGF1α were found in the effluent. The most drastic developmental change was the increase in the amount of 15-keto-metabolites of PGE2 from late fetal period to the lungs of one day old rabbits (1.8 fold increase between birth and first postnatal day). Smaller changes were detected in the amounts of other cyclo-oxygenase products. 相似文献
13.
Toshihiro Hidaka Patrick Y-K Wong Kafait U Malik 《Prostaglandins & other lipid mediators》1980,19(5):805-818
Infusion of [14C] arachidonic acid (AA) into the isolated, Tyrode perfused rabbit spleen resulted in the release of a substance into the venous effluent with the musculotropic activity and chromatographic properties of prostaglandin (PG)E2. Smaller amounts of radioactive materials with the chromatographic properties of PGF2α, 6-keto-PGF1α, and PGD2 were also released. The radiolabeled material released in largest amounts from the spleen was identified as PGE2 on the basis of: 1) Co-chromatography with PGE2 in three solvent systems, 2) Conversion of the radioactive material and of authentic [3H] PGE2 to similar products by treatment with sodium borohydride and with potassium hydroxide, and 3) Stability of the musculotropic activity in Tyrode solution at 37°C. Release of the major and minor radioactive products was inhibited by pretreatment of the spleen with either indomethacin or 5,8,11,14-eicosatetraynoic acid. 相似文献
14.
Ray V. Haning Francis X. Kieliszek Sandra P. Alberino Leon Speroff 《Prostaglandins & other lipid mediators》1977,13(3):455-477
Antibodies to the 13,14-dihydro-15-keto metabolite of prostaglandin F2α(PGF2αM) were raised in sheep using a bovine thyroglobulin conjugate of PGF2αM. Labeled 13,14-dihydro-15-keto prostaglandin A2 (PGA2M), 13,14-dihydro-15-keto prostaglandin E2 (PGE2M) and PGF2αM were prepared from their corresponding high specific activity parent prostaglandins with swine kidney homogenate and purified using reverse phase liquid-liquid partition chromatography. A rapid method of column chromatography for use prior to radioimmunnoassay was developed.Mathematical corrections for the effect of recovery tracer on the logit/log transformation are presented with a new approach to expression of radioimmunoassay cross reactions allowing continuous expression of the variation of these cross reactions with displacement. These mathematical approaches are widely applicable to other radioimmunoassay systems and transformations.The assay was used for measurement in groups of human volunteers: males, females, women at delivery and paired venous umbilical cord bloods. A correlation between venous cord and maternal peripheral PGF2αM levels is demonstrated with a gradient from the cord plasma to maternal plasma. 相似文献
15.
Yao-Fa Li Hongwei Zhang Joseph A. RingbauerJr Cynthia L. Goodman Tamra Reall Lincoln Kaile Zhou David Stanley 《In vitro cellular & developmental biology. Animal》2017,53(5):421-429
Prostaglandins (PGs) are oxygenated metabolites of arachidonic acid (AA) and two other C20 polyunsaturated fatty acids that serve as biochemical signals mediating physiological functions. We reported that PGs influence protein expression in insect cell lines, which prompted the question: do PGs influence cell proliferation or viability in insect cell lines? Here, we report on the outcomes of experiments designed to address the question in cell lines from three insect orders: Hemiptera (squash bug, Anasa tristis, BCIRL-AtE-CLG15A), Coleoptera (red flour beetle, Tribolium castaneum, BCIRL-TcA-CLG1), and Lepidoptera (tobacco budworm, Heliothis virescens, BCIRL-HvAM1). Treating the insect cell lines with PGA1, PGA2, or PGD2 led to dose-dependent reductions in cell numbers. All three cell lines were sensitive to PGA1 and PGA2 (IC50s = 9.9 to 26.9 μM) and were less sensitive to PGD2 (IC50s = 31.6 to 104.7 μM). PG treatments also led to cell death at higher concentrations, as seen in mammalian cell lines. PGE1, PGE2, and PGF2α treatments did not influence AtE-CLG15A or HvAM1 cell numbers at lower concentrations, but led to dose-related reductions in TcA-CLG1 cells at higher concentrations. Similar treatments with pharmaceutical inhibitors of PG biosynthesis also led to reduced cell numbers: MAFP (inhibits phospholipase A2), indomethacin (inhibits PG biosynthesis), and esculetin (inhibits lipoxygenase). Because these pharmaceuticals are used to relieve inflammation and other medical issues in human medicine, they are not toxic to animal cells. We infer PGs are necessary in optimal quantities for ongoing homeostatic functions in established cell lines; in quantities outside the optimal concentrations, PGs are deleterious. 相似文献
16.
The ability of various prostaglandins (PGs) to affect the anamnestic immune response of keyhole limpet hemocyanin (KLH)-primed rabbit popliteal lymph node cells was investigated. Of the four PGs studied (PGA1, PGE2 and PGF2α), PGE1 was found to have a stimulatory effect, whereas PGA1, PGE2 and PGF2α were ineffective in stimulating or inhibiting the anamnestic response. Under the conditions studied, a 3.5-fold increase in antibody production was obtained in PGE1-treated, KLH-stimulated cultures. Maximum enhancement was obtained when 0.2 μg of PGE1 were added at the time of culture initiation and were allowed to remain in contact with the lymph node cells for 24 hours. 相似文献
17.
Metabolism of prostaglandin A. I. The kidney cortex as a major site of PGA2 degradation 总被引:2,自引:0,他引:2
The antihypertensive and natriuretic prostaglandin A2 (medullin) has been isolated and identified in rabbit renal papilla. Since PGA2, unlike prostaglandin F2 (PGE2) and prostaglandin F2α (PGF2α), is not metabolized by the lung, studies were undertaken to determine if the site of PGA2 metabolism is in the renal cortex where its primary vasodilatory and natriuretic effects occur. In experiments, homogenates of renal cortex and outer medulla were incubated with 3H-PGA2 (0.2 μc, 20 μg) at 37°C for 30 minutes. A metabolite(s) less polar than 3H-PGA2 was observed following silicic acid chromatography of acidic lipid extracts of cortical, but not outer medullary homogenates. In studies, 3H-PGA2 (2 μc, 50 μg) was injected into the renal artery of the rabbit and blood withdrawn from the ipsilateral renal vein. At least three less polar major metabolites of PGA2 were observed in the plasma within 15 seconds following injection. No appreciable 3H-PGA2 was observed in venous plasma 30 seconds following injection of 3H-PGA2. In contrast to plasma, the major urinary metabolites were more polar than PGA2. The present study reveals that PGA2 is almost completely metabolized in a single passage through the rabbit kidney suggesting this organ is a major site of PGA2 metabolism. 相似文献
18.
Frances A. Kimball Kenneth T. Kirton Lillian J. Wyngarden 《Prostaglandins & other lipid mediators》1975,10(5):853-864
Myometrial low speed supernatant prepared from non-pregnant rhesus uteri was incubated with 3H-Prostaglandin (PG)E1 with or without addition of unlabelled prostaglandins. The uptake of 3H-PGE1 was inhibited in a dose dependent fashion by PGE2>PGE1>PGA1>PGF2α=PGA1>PGB1=PGB2≥PGD2. PGE1 metabolites inhibited 3H-PGE1 binding in the following order: 13,14-dihydro-PGE1>13,14-dihydro-15-keto-PGE1=15-keto-PGE1. The specific binding of 3H-PGE1 and 3H-PGF2α was similarly affected by the temperature and time of incubation. Equilibrium binding constants determined using rhesus uteri obtained during the luteal phase of the menstrual cycle indicate the presence of high affinity PGE1 binding sites with an average (n=3) apparent dissociation constant of 2.2 × 10−9M and a lower affinity PGE1 binding site with a Kd ≅ 1 × 10−8M. No high affinity — low capacity 3H-PGF2α sites could be demonstrated.Relative uterine stimulating potencies of some natural prostaglandins and prostaglandin analogs tested after acute intravenous administration in mid-pregnant rhesus monkeys corresponded with the PGE1 binding inhibition of the respective compound. The uterine stimulating potencies of the prostaglandin analogs tested were: (15S)-15-methyl-PGE2=16,16-dimethyl-PGE2>17-phenyl-18,19,20-trinor-PGE2>16 phenoxy-17,18,19,20-tetranor-PGF2α=PGE2=PGE1=(15S)-15-methyl-PGF2α>PGF2α. 相似文献
19.
Human serum binds PGA1 > PGE1 > PGF2α. This is in inverse order of their polarity. Approximately 90% of PGA1 is bound. By analogy with steroid and iodothyronine metabolism, it is likely that the tighter binding of PGA1 accounts for its relatively slow clearance. 相似文献
20.
H. Thaler-Dao M. Ramonatxo M. Saintot J. Chaintreuil A.Crastes de Paulet 《Prostaglandins & other lipid mediators》1982,24(2):149-163
prostaglandin biosynthesis by uteri of ovariectomized rats and guinea pigs treated or untreated with oestradiol 17 β, administered subsutaneously, was measured by R.I.A. of PGF2α and PGE2. Incubations with [1-14C] arachidonic acid were also performed and labelled metabolites were analyzed by TLC. The main metabolite in rats was 6 keto PGF1α and in decreasing order of magniture, PGF2α and PGE2. In guinea pig PGF2ga was the main product. Ovariectomy in rats completely changed the pattern of synthesized prostanoids: PGI2 production was doubled when compared to cycling rats and PGE2 increased 10 fold. PGF2α walues were similar to the mean value measured during the cycle. OE2 treatment almost completely inhibited PGI2 synthesis and reduced PGE2 by half. Total PG synthesis in OE2 treated animals was decreased by 5 fold when compared to spayed rats. Endogenous PGFsα synthesis was slightly stimulated. In the guinea pig OE2 treatment of ovariectomized animals increased the total synthesis from 50 per cent. PGF2α was always the main metabolite. In conclusion OE2 regulation of uterine PG synthesis is depending on the animal species and cannot be explained by a unique effect on the cyclooxyhenase, but rather by an interplay on the various enzymes of the arachidonic acid cascade. 相似文献