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1.
Cervical connective tissue was obtained from non pregnant fertile women undergoing hysterectomy. Tissue specimens were mechanically chopped into 1 mm thick slices which were preincubated in Krebs-Ringer bicarbonate buffer containing PGE2 or PGF (300 ng/ml). After 60 min the slices were transferred into fresh buffer with the corresponding PG-concentration and 3H-labelled proline or hydroxyproline. Following incubation (60 min) the protein bound radioactivity was determined and related either to the dry weight or to the protein content of each slice. The two methods used did not show any qualitative differences. The experiments showed that PG:s had a marked effect on protein synthesis in the cervical tissue. During the follicular phase incubation with both types of PG:s was followed by a decreased incorporation indicating decreased net synthesis of collagen while there was an increased incorporation and hence increased synthesis in the luteal phase. There was no significant influence on the distribution of the model amino acid 14C-AIB in the presence of PG:s neither in the follicular nor in the luteal phase. The present data point to an acute effect of PGE2 and PGF on cervical collagen metabolism and indicate furthermore that the process is steroid hormone dependent. It is concluded that these substances may exert their effect by modulating the incorporation of amino acids into protein.  相似文献   

2.
The in vitro effects of a stable PGE-analogue (9-deoxo-16, 16-dimethyl-9-methylene PGE2 (9-methylene PGE2) on human cervical tissue was investigated. The influence of the analogue on collagen biosynthesis was studied by measuring the incorporation of 3H-proline, while smooth muscle effects were evaluated by isometric recording of contractile activity. The specimens were obtained by needle biopsy from women in early and late pregnancy and from nonpregnant women of fertile age.9-methylene PGE2 compared with controls increased the incorporation of 3H-proline in the secretory phase and before the 9th week of pregnancy, whereas radiolabelling was decreased in the follicular phase, in the 9th–12th week and at term. With respect to incorporation of 3-H-proline, 9-methylene PGE2 was equipotent to PGE2. 9-methylene PGE2 inhibited spontaneous contractile activity in early as well as in late pregnancy but increased muscular activity in nonpregnant patients. The inhibitory effects of the analogue was similar to that of PGE2 but the natural compound was considerably more potent in this respect.  相似文献   

3.
Suspensions of dispersed bovine luteal cells prepared by collagenase digestion of luteal tissue specifically bound [3H]Prostaglandin (PG) E1 and [3H]PGF. While the number of sites per cell (~ 1.8 × 105) were about the same for both [3H]PGs, the apparent Kds were different: [3H]PGE1 ? 2.4 nM; [3H]PGF ? 11 nM. The [3H]PGs binding was inhibited in a dose-dependent manner in the presence of increasing concentrations of unlabeled PGs. Potency order for inhibition of [3H]PGE1 binding was: PGE2 > PGE1 > PGF > PGF. The corresponding data for [3H]PGF was: PGF > PGF > PGE2 > PGE1. While [3H]PGE1 and [3H]PGF bind to their own receptors with high affinity, their affinities for each other's binding were extremely low. Thus, these results demonstrate that luteal cells, like plasma membranes isolated from luteal tissue, contain receptors for PGEs and PGF which are discrete with respect to specificity and affinity.  相似文献   

4.
(3H) PGE2 uptake and transfer in the isolated perfused human placental cotyledon was assessed by a ingle pass paired isotope dilution technique utilising (14C) sucrose as an extracellular marker. Metabolism of (3H) PGE2 was measured by analysing maternal and fetal effluents from perfused human placental cotyledons after bolus injection of (3H) PGE2 into ither the maternal or fetal sides. Maximal uptake of (3H) PGE2 was greater on the maternal (81 +/- 8%) than the fetal sides (42 +/- 12%) and showed saturation with increasing concentrations of PGE2 only on the fetal side with an apparent Km of 12 +/- 4.9 nmol/l and vmax of 1.5 +/- 0.2 pmol/min/g. Total recoveries of (3H) PGE2 were 84.6 +/- 11.8 % and 32.6 +/- 6.3 % of the injected dose after injection on the fetal and maternal sides respectively.Transferof (3H) PGE2 was the same in both directions being 6.4 +/- 1.2 % of the injected dose in the fetal-maternal direction and 5.8 +/- 2.7 % of the injected dose in the maternal-fetal direction. Metabolism was greater on the maternal side (35% of injected (3H) PGE2) thanthe fetalside(18% of injected (3H) PGE2) and was principally to the 13,14-dihydro-15-keto-PGE2 metabolite. Metabolism of (3H) PGE2 after passage across the placenta was the same in both directions and was of the order of approximately 60%.  相似文献   

5.
In the present investigation, a hCG sensitive glycosyl-phosphatidylinositol (GPI) was isolated from cultured rat granulosa cells obtained from the ovaries of diethylstilbestrol (DES) implanted immature rats. The inositol-phosphoglycan (IPG) moiety of the GPI-lipid contains galactose, glucosamine, and myoinositol as demonstrated by metabolic labelling of granulosa cells for different time periods (5–96 h) with [3H]galactose, [3H]glucosamine, or [3H]myoinositol and treatment of the purified [3H]GPI with phosphatidylinositol-specific phospholipase C. Labelling equilibrium of the GPI-lipid was achieved after 24 h ([3H]galactose and [3H]myoinositol) or 72 h ([3H]glucosamine) incubation, whereas incorporation of other labelled carbohydrates tested ([3H]galactosamine, [3H]mannose, and [3H]sorbitol) was negligible throughout the time period studied. The glucosamine C-1 appears to be linked through a glycosidic bond to the myoinositol molecule of the IPG moiety as revealed by the generation of phosphatidylinositol (PtdIns) after nitrous acid deamination of dual labelled ([3H]glucosamine/[14C]palmitate or [3H]glucosamine/[14C]myristate) glycosyl-phosphatidylinositol. To investigate the fatty acid composition of the diacylglycerol (DAG) backbone of the GPI, granulosa cells were also labelled (5–72 hr) with [14C]linoleate, [3H]myristate, [3H]-oleate, [3H]palmitate, or [3H]stearate and the radioactivity associated with the purified glycosyl-phosphatidylinositol determined. Incorporation of [3H]palmitate and [3H]myristate into the GPI-lipid peaked after 8 h and 24 h of labelling, respectively, and both fatty acids were partially released after PLA2 treatment of the dual labelled ([3H]glucosamine/[14C]palmitate or [3H]glucosamine/[14C]myristate) GPI. In parallel experiments no significant incorporation of labelled stearate, oleate, or linoleic acid into the DAG backbone of the glycosylphosphatidylinositol could be detected. Granulosa cells were also labelled with [3H]glucosamine in the presence of FSH (30 ng/ml), cholera toxin (1 μg/ml), or the membrane permeable cAMP analog (but)2 cAMP (1 mM). Time related increases in GPI-labelling were apparent after 48 h and reached a maximum level (3-, 5-, and 7-fold for FSH, CT, and (but)2 cAMP, respectively) after 72 h in culture. In another set of experiments, granulosa cells were labelled for 72 h with [3H]glucosamine in the presence of (but)2cAMP (1 mM), TPA (10?7 M), or combination thereof. The effect of treatment with the membrane permeable cAMP analog on GPI labelling was prevented in the presence of TPA, whereas no differences in [3H]GPI content could be observed in untreated granulosa cells or cells cultured in the presence of the protein kinase C-activating phorbol ester alone. In cells differentiated with FSH (30 ng/ml for 3 days) to induce LH receptors, treatment with hCG (100 ng/ml) induced a rapid (60 sec) and transient (5 min) decrease in the GPI content, whereas no efect of the hormone on undifferentiated granulosa cells could be observed. The rapid effect elicited by hCG on GPI content and turnover may be an early transduction mechanism involved in the biological effects of LH/hCG in differentiated granulosa cells. © 1993 Wiley-Liss, Inc.  相似文献   

6.
The fetus and prematurely delivered newborn lamb have high concentrations of circulating PGE2 that may play a hormonal role, particularly in maintaining the patency of the ductus arteriosus. We studied the ability of the isolated, perfused lung from immature (100 ± 150 days) lamb fetuses to metabolize PGE2 as a function of PGE2 concentration in the perfusate. After an intra-arterial infusion of 3H-PGE2 and 14C-inulin (to act as a marker of extracellular space), the bulk of the 14C-inulin was rapidly cleared through the isolated lung and the majority of the 3H activity appeared after the 14C activity had fallen to negligible values. The 3H activity that was retained longer in the lung was primarily associated with the 15-keto prostaglandin E2 and 15-keto-13,14 dihydro prostaglandin E2 metabolites. Lungs from immature fetal lambs metabolized 25% less PGE2 than did lungs from animals near term. This is consistent with our prior observation that premature lambs have decreased plasma clearance rates (in vivo) and elevated circulating concentrations of PGE2 when compared with term newborn lambs.  相似文献   

7.
We examined the effect of prostaglandin E2 (PGE2), in the presence or absence of cortisol, on bone formation in 21-day fetal rat calvaria maintained in organ culture for 24 to 96 h. [3H]Thymidine and [3H] proline incorporation were used to assess DNA and collagen synthesis, respectively. Changes in dry weight and DNA content were assessed after 96 h.PGE2 (10−7 M) stimulated both DNA and collagen synthesis in calvaria. The effect on DNA synthesis was early (24 h), transient and limited to the periosteum. Collagen synthesis was stimulated at a later time (96 h), predominantly in the central bone. Cortisol (10−7 M) inhibited DNA and collagen synthesis. The addition of PGE2 reversed the inhibitory effects of cortisol on DNA synthesis and content and increased collage synthesis in central bone to levels above control untreated cultures.We conclude that PGE2 has stimulatory effects on bone formation and can reverse the inhibitory effects of cortisol. Hence the effects of cortisol may be mediated in part by their ability to reduce the endogenous production of prostaglandins.  相似文献   

8.
Uteri, ovaries and oviducts from mice were collected at autopsy. Tissue slices were incubated with [3H]-PGE2 in the presence or absence of a large excess (100 fold) of nonradioactive PGE2 using 0.01M sodium phosphate buffer (pH 7.2). Bound and free PGs were separated by a filtration technique. PGE2 accumulation by the uteri was evaluated as a function of incubation time, wet weight of tissues, and reproductive state. The tissue to medium ratio (T/M) was greater than 1.0 for uteri as the time of incubation increased. This suggests the presence of PGE2 binding sites in mouse uterine tissue. Also, PGE2 accumulation was not observed in oviducts or in ovaries.  相似文献   

9.
Patterns of arachidonic acid release and metabolism were altered in human synovial fibroblasts following exposure to cytokines. Recombinant interleukin-1 induced an approximate 3-fold in crease in [3H]-AA release, a 7-fold increase in PGE2 production and a 2-fold increase in PLA2 activity in human synovial fibroblasts. Recombinant tumor necrosis factor induced similar responses, however, the magnitude was less than that mediated by interleukin-1. A combination of the two cytokines had an additive effect on [3H]-AA release and PLA2 activity while PGE2 production was similar to that detected using interleukin-1 alone. [3H]-AA, was released in substantial amounts when sodium fluoride was used as a stimulus but PGE2 was not. These data show that tumor necrosis factor and interleukin-1 can both activate synovial cell PLA2 and induce generation of PGE2, but act in an additive rather than a synergistic fashion. Furthermore, the data show that PGE2 production is not always concordant with [3H]-AA release, suggesting that appropriate enzyme(s) must be activated.  相似文献   

10.
The effect of 7-fluoro proscyclilin (PGI2-F), a chemically stable analogue of prostacyclin, on cAMP accumulation in and [3H]PGE binding to mastocytoma P-815 cells was compared with those of the Na salt and methyl ester of prostacyclin (PGI2Na or PGI2Me), which are rapidly inactivated in aqueous solution or metabolized in the tissue.PGIF was as effective as PGI2Me, and slightly less effective than PGI2Na in stimulating cAMP accumulation in mastocytoma cells and rabbit platelets. PGI2F was also more stable than PGI2Me or PGI2Na, and retained its original cAMP elevating activity even after incubation with or without cells for 4 h at 37°C. Cells which had been exposed to PGI2F and then washed free of unbound reagent continued to produced cAMP for more than 3 h. PGI2F was also as effective as PGE1 or PGE2 in displacing [3H]PGE2 bound to the cells. Non-competitive inhibition by PGI2F or PGI2Me of [3H]PGE2 binding to the cells, with apparent Kis of 1.29 μM and 1.13 μM, respectively, indicates the presence of different receptors for PGE2 and for PGI2F or PGI2Me in mastocytoma P-815 cells.  相似文献   

11.
Prostaglandins E1 and E2 are thought to be inhibitors of the growth of systemic vascular smooth muscle cells (SMC). However, their effect on the proliferation of SMC from the pulmonary artery (PA) has not been described and was the subject of this investigation. Cultures of bovine PA SMC were exposed to PGE1 and PGE2 under various conditions and their growth was assessed. PGE1 and PGE2 did not inhibit the growth of PA SMC in 10% fetal calf serum (FCS), but instead caused a dose dependent (10 ng - 1 μg/ml) increase in [3H]-thymidine incorporation when added to cultures containing 0.5% FCS; the highest doses resulted in 95% and 75% increases in [3H]-thymidine uptake at 24 hours with PGE1 and PGE2 respectively. This was accompanied by a modest increase in actual cell numbers (e.g., 20% with 1 μg/ml PGE1). Furthermore, PGE1 could mimic insulin-like growth factor (IGF-1) by potentiating the stimulation of SMC growth by fibroblast growth factor, suggesting that PGE1 may act as a progression factor in the growth cycle of these cells. There was, however, no effect of PGE1 on the proliferation of bovine aortic SMC. We conclude that, contrary to most reported effects on systemic SMC, PGE1 and PGE2 do not inhibit the proliferation of PA SMC but rather stimulate it.  相似文献   

12.
This study examined the ability of various drugs to modify the potassium (K) or d-amphetamine (d-A) induced release of 3H-norepinephrine 3HNE) from chopped rat cortical tissue. The K induced release of the transmitter, which occurs from reserpine sensitive sites of cortical tissue, was significantly reduced by the beta receptor antagonist propranolol, the alpha receptor agonist clonidine and also by PGE2. Pretreatment with eicosatetrynoic acid, an inhibitor of prostaglandin synthesis, did not influence the effect of clonidine on 3HNE release; thus this latter effect appears to be independent of enhanced prostaglandin formation. The proposed alpha receptor mediated negative feedback exhibits stereospecificity since addition of exogenous 1-, but not d-, NE decreased release of the transmitter. Blockade of alpha receptors by phentolamine or stimulation of beta receptors by isoproterenol significantly enhanced the K induced release of 3HNE from cortical tissue. By contrast, the d-A induced release of 3HNE which occurs from reserpine-insensitive sites, was reduced by propranolol and clonidine; and was not altered by phentolamine, isoproterenol or PGE2. These data indicate that the K, but no d-A, induced release of 3HNE from cortical tissue is modified in accordance with postulated presynaptic negative and positive feedback mechanisms.  相似文献   

13.
The objective of these experiments was to determine the fate of tritium from the 5 position of proline and to assess the validity of its loss to H2O as a measure of proline oxidation. When [5-3H]proline was fed to barley (Hordeum vulgare) leaves, tritium was recovered in H2O and metabolites such as glutamate, glutamine, organic acids, aspartate, asparagine, and γ-aminobutyrate. Collectively these metabolites, which are oxidation products of proline, accounted for 8% of the 3H recovered after 5 hours. In spite of the amount recovered in metabolites, the rates of proline oxidation estimated by measuring 3H2O recovery from [5-3H]proline were only slightly lower than rates estimated by incorporation of 14C into oxidized products and loss of 14C from total proline. Therefore, 3H2O recovery from [5-3H]proline is useful in assessing the effects of stress on proline metabolism.

Water stress inhibited proline oxidation, as reported previously. In addition, a reconversion of proline oxidation products to proline occurred in stressed leaves. This observation probably indicates a breakdown in cellular compartmentation of proline synthesis and proline oxidation.

  相似文献   

14.
Thymocytes which have developed in the C3H thymus showed depressed proliferative responses to stimulation with anti-CD3 antibody as compared with those which have developed in the thymus of other strains of mice (i.e. AKR). The present study was conducted to analyze immunological functions of the thymic stromal cell population (low-density adherent cells, LDAC) in the C3H mice using allogeneic bone marrow (BM) chimeras established by BM transplantation in the reciprocal combination of AKR and C3H mice as donor or recipient. The thymic LDAC from C3H mice or the [AKR(donor)→C3H(recipient)] chimeras contained a high proportion of Mac-1+ cells as compared to AKR mice or the [C3H→AKR] chimeras. The proportion of Mac-1+ cells paralleled the IL-1- and PGE2-secreting ability of the LDAC cultured either in the presence or absence of LPS and also paralleled the antigen-presenting cell functions of the LDAC. Furthermore, after anti-CD3 stimulation the PGE2 inhibited more profoundly proliferative responses of [AKR→C3H] or normal C3H thymocytes than those of the [C3H→AKR] chimera or normal AKR thymocytes. A PGE2 inhibitor, indomethacin, reversed the depressed responses of the thymocytes which had developed in the C3H thymus. These findings suggest that the lower responsiveness of thymocytes from [AKR→C3H] chimeras to anti-CD3 stimulation may be attributable to large amounts of PGE2 secreted by LDAC and/or to increased sensitivity of thymocytes themselves to PGE2.  相似文献   

15.
1. When pig ear skin slices were cultured for 18h in the presence of 1μg of tunicamycin/ml the incorporation of d-[3H]glucosamine into the epidermis, solubilized with 8m-urea/5% (w/v) sodium dodecyl sulphate, was inhibited by 45–55%. This degree of inhibition was not increased by using up to 5μg of tunicamycin/ml or by treating the skin slices with tunicamycin for up to 8 days. The incorporation of (U-14C)-labelled l-amino acids under these conditions was not affected by tunicamycin. Polyacrylamide-gel electrophoresis indicated that the labelling of the major glycosaminoglycan peak with d-[3H]glucosamine was unaffected, whereas that of the faster migrating glycoprotein components was considerably decreased in the presence of tunicamycin. 2. Subcellular fractionation indicated that tunicamycin specifically inhibited the incorporation of d-[3H]glucosamine but not of (U-14C)-labelled l-amino acids into particulate (mainly plasma-membrane) glycoproteins by about 70%. The labelling of soluble glycoproteins was hardly affected. Polyacrylamide-gel electrophoresis of the plasma-membrane fraction showed decreased d-[3H]glucosamine incorporation into all glycoprotein components, indicating that the plasma-membrane glycoproteins contained mainly N-asparagine-linked oligosaccharides. 3. Cellulose acetate electrophoresis of both cellular and extracellular glycosaminoglycans showed that tunicamycin had no significant effect on the synthesis of the major component, hyaluronic acid. However, the incorporation of both d-[3H]glucosamine and 35SO42− into sulphated glycosaminoglycans was inhibited by about 50%. This inhibition was partially overcome, at least in the cellular fraction, by 2mm-p-nitrophenyl β-d-xyloside indicating that tunicamycin-treated epidermis retained the ability to synthesize sulphated glycosaminoglycan chains. Tunicamycin may affect the synthesis and/or degradation of proteoglycan core proteins or the xylosyltransferase. 4. Electron-microscopic examination of epidermis treated with tunicamycin for up to 4 days revealed no significant changes in cell-surface morphology or in epidermal-cell adhesion. Either N-asparagine-linked carbohydrates play little role in epidermal-cell adhesion or more probably there is little turnover of these components in epidermal adhesive structures such as desmosomes and hemidesmosomes during organ culture.  相似文献   

16.
The effect of prostaglandin E2 (PGE2) on fibroblast proliferation was examined. The presence of PGE2 for 24 h inhibited the growth of quiescent cells stimulated with serum, platelet-derived growth factor and macrophage-derived factors. Maximal inhibition of nuclear labeling with [3H]thymidine occurred at concentrations greater than 10−7 M. The inhibitory effect of PGE2 was less potent in exponentially growing cells and was not the result of conversion of PGE2 to PGA2 during incubation in growth medium. The G1 phase was determined to be 12–14 h in untreated cultures. The extent of growth inhibition by PGE2 was similar with addition of PGE2 at 0, 3, 6, or 9 h following restimulation of quiescent cell cultures. Approximately 25% of the cells that enter S phase are refractory to PGE2-induced growth inhibition. Short-term exposure to PGE2 (5 min and 30 min) caused substantial growth inhibition. The serum-induced proliferation was also inhibited by the cAMP analogue, dibutyrl cAMP. Our results suggest that PGE2 affects a distinct subpopulation of cells. Restimulation of quiescent cells treated with PGE2 for 24 h, indicated that release from PGE2 exposure is associated with prolongation of the G1 phase of the cell cycle.  相似文献   

17.
C V Rao 《Life sciences》1977,20(12):2013-2022
Pretreatment of membranes for 1 hr at 4° with up to 0.1% Triton X-100 (TX-100) and sodium desoxycholate (SDC), resulted in a greater loss of [3H] prostaglandin (PG)F2α binding compared to E1 binding. Lubrol WX (LWX) tended to cause a greater loss of [3H]PGF2α than E1 binding. However, the differential loss was not as marked as with TX-100 or SDC. Triton X-305 was relatively ineffective, but loss of [3H]PGE1 binding was greater than for PGF2α. Increasing concentrations of dimethylsulfoxide (DMSO) progressively inhibited PGF2α binding without affecting PGE1 binding. The detergent, but not DMSO, induced losses of membrane PG binding were due to solubilization of the receptors. Greater amounts of membrane protein and phospholipids were solubilized at detergent (TX-100 and SDC) concentrations that solubilized 100% of PGE1 receptors compared to 100% solubilization of F2α receptors. Neither the duration of preincubation nor the amount of membrane protein chosen were responsible for differential PGE1 and F2α receptor losses. These differential membrane PG receptor losses raise the possibility of differences in PGE1 and F2α receptors association with the membrane structure.  相似文献   

18.
[3H]Prostaglandin (PG) E2 bound specifically to several subcellular fractions from bovine myometrium. The binding was temperature dependent, rapid, and reversible. PGE2 and PGE1 competed for the [3H]PGE2 binding site. The PGs inhibited in the following decreasing order: PGE2 = PGE1 ? PGF > PGA2 > PGF > PGB2. No competitive effect could be found for oxytocin. Scatchard analysis of the binding data were interpreted as showing a single high-affinity binding constant. There was no difference in the binding constant between the various fractions. The average molar dissociation constant was 2.74 ± 0.14 × 10?9. Quantitative differences in the maximum number of binding sites were observed between fractions. One plasma membrane fraction contained 21.4 ± 2.3 × 10?11 and the sarcoplasmic reticulum contained 11.2 ± 0.8 × 10?11 mol binding sites/g. The results suggest that there is a high-affinity PGE2 receptor present in both plasma membrane and sarcoplasmic reticulum.  相似文献   

19.
The effects of exogenous histamine (H) on prostaglandin (PG) generation and release in uteri isolated from diestrous rats and the influences of H2-receptors blockers (cimetidine and mitiamide) on the output of uterine PGs, were explored. Moreover, the action of H on the uterine 9-keto-reductase, was also studied. Histamine (10−4M) failed to alter the basal output of PGE1 but reduced significantly the generation and release of PGE2 and augmented the output of PGF. On the other hand, cimetidine (10−5M) enhanced the basal release of PGE2 but had no action on the outputs of PGs E1 or F. The enhancing effect of H on the production and release of PGF was abolished in the presence of cimetidine. Also, the antagonist reversed the influence of H on the output of PGE2. Metiamide, another H2-receptor antagonist, did not alter the basal control generation and release of uterine PGs, but antagonized the augmenting influence of H on PGF uterine output, as much as cimetidine did, and prevented the depressive action of H on the release of PGE2 from uteri. Histamine (10−4M) significantly stimulated uterine formation of cyclic-adenosine monophosphate, an action which was antagonized by the presence of cimetidine (10−5M), a blocker of H2 receptors. Also, histamine (10−5M) and dibutyril-cyclic-adenosine monophosphate (DB-cAMP) at 10−3M, enhanced significantly the formation 3H-PGF from 3H-PGE2. Results presented herein demonstrate that H is able to diminish the generation of PGE2 in uteri from rats at diestrus augmenting the synthesis of PGF, apparently via the activation of H2-receptors, enhancing adenylate-cyclase. These effects appear to increase uterine 9-keto-reductase activity which transforms PGE2 into PGF. Relationships between the foregoing results and those evoked by estradiol, are also discussed.  相似文献   

20.
The possibility that prostaglandins could serve as substrates for the guinea pig adrenal microsomal monooxygenase was investigated. The binding of PGE1 to adrenal microsomes was found to exhibit a reverse type I spectral change. Also PGE1 diminished the magnitude of type I spectrum elicited by cortisol binding to adrenal microsomes. The incubation of [3H]PGE1 or of [3H]PGE2 with adrenal microsomes supplemented with NADPH yielded primarily the respective 19-hydroxy metabolite. The enzymatic activity catalyzing this hydroxylation appears to be a typical monooxygenase, requiring NADPH for activity and being strongly inhibited by metyrapone, SKF 525A, and cytochrome c. Carbon monoxide at a ratio of 9:1 to oxygen moderately inhibited the hydroxylation of PGE1. Whereas the liver catalyzed the hydroxylation of PGE1 and PGA1 equally well, the adrenal microsomes preferentially catalyzed the hydroxylation of PGE1. This finding and the observation that α-naphthoflavone is a weak inhibitor of the adrenal PGE1 hydroxylation points to significant differences between the adrenal and liver prostaglandin hydroxylation activities. Cortisol, which is a substrate for adrenal monooxygenase, strongly inhibited PGE1 and PGE2 hydroxylation. By contrast, certain xenobiotics (ethylmorphine, hexobarbital, benzpyrene), which are also metabolized by adrenal microsomes, only slightly inhibited the hydroxylation of PGE1. Similarly, PGE1 only weakly inhibited ethylmorphine and benzphetamine demethylation and hexobarbital hydroxylation. These observations suggest that adrenal microsomes contain several monooxygenases with different affinities for prostaglandins and for the different xenobiotic substrates.  相似文献   

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