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PubMed1988

RU486 inhibits induction of aromatase by dexamethasone via glucocorticoid receptor in cultured human skin fibroblasts.

Effects of RU486 on the induction of aromatase by dexamethasone via glucocorticoid receptor were determined using cultured human skin fibroblasts. Competition of [3H]dexamethasone binding to the cytosol receptor was 7 times stronger with RU486 than with dexamethasone. The order of the strength of competition was RU486 greater than dexamethasone greater than betamethasone greater than prednisolone greater than hydrocortisone. RU486 abolished a specific 8.6 S [3H]dexamethasone binding peak in the cytosol, determined using a sucrose density gradient analysis. Dexamethasone markedly induced aromatase and this event was strongly suppressed by RU486, in a dose-dependent manner, in the cultured skin fibroblasts. A linear correlation between the strength of competition and the induction of aromatase of various glucocorticoids was observed. RU486 non-competitively inhibited aromatase induction by dexamethasone determined from a double reciprocal plot of aromatase activity, with respect to [3H]androstenedione concentration in the presence of RU486. These results show that RU486 is a peripheral noncompetitive antiglucocorticoid on aromatase induction by glucocorticoid in human skin fibroblasts and that aromatase induction is a good marker for the biological function of glucocorticoid receptor in human skin fibroblasts.

Aromatase Inhibitors↗
PubMed1994

The overnight dexamethasone test is the procedure of choice in screening for Cushing's syndrome.

This study was undertaken to examine the performance of the overnight dexamethasone test, i.e., plasma cortisol level at 8-9 AM following dexamethasone 1 mg by mouth at midnight, in screening for Cushing's syndrome. The participants included 19 patients with Cushing's syndrome (17 with Cushing's disease, 1 with adrenal carcinoma, and 1 with ectopic ACTH syndrome) and 96 patients in whom the possibility of Cushing's syndrome was raised but who did not have the disorder. Utilizing our original very conservative cutoff point of plasma 100 nmol/L (3.62 micrograms/dL) above which Cushing's syndrome was suspected, the sensitivity of the test was 100% but the false positive rate was an unsatisfactory 12.5%. However, the lowest plasma cortisol level achieved following the overnight dexamethasone test in patients with Cushing's syndrome was 259 nmol/L (9.39 micrograms/dL). A plasma cortisol cutoff point of 250 nmol/L (9.06 micrograms/dL) yielded no false negatives and the false positive rate fell to 6.25%. Using a cutoff point of 200 nmol/L (7.24 micrograms/dL) the false positive rate was 7.3%. These performance characteristics of the overnight dexamethasone test compare very favorably with the reported experience of all other screening procedures for Cushing's syndrome including the urinary free cortisol excretion rate and the 48 h dexamethasone test, while the overnight dexamethasone procedure is the simplest for both patients and medical personnel. Since it is possible that some very unusual patients may suppress to plasma cortisol levels lower than that seen in the present study, we now recommend the overnight dexamethasone test using a plasma cortisol cutoff point of 200 nmol/L as the procedure of choice when screening for patients with Cushing's syndrome.

ACTH Syndrome, Ectopic↗
PubMed1984

The effects of dexamethasone on palate mesenchymal cell phospholipase activity.

Corticosteroids will induce cleft palate in mice. One suggested mechanism for this effect is through inhibition of phospholipase activity. This hypothesis was tested by measuring the effects of dexamethasone, a synthetic corticosteroid, on phospholipase activity in cultures of palate mesenchymal cells. Palate mesenchymal cells were prelabeled with [3H]arachidonic acid. The cells were subsequently treated with various concentrations of dexamethasone. Concurrently, cultures of M-MSV-transformed 3T3 cells were prepared identically. After treatment, phospholipase activity was stimulated by the addition of serum or epidermal growth factor (EGF), and radioactivity released into the medium was taken as a measure of phospholipase activity. Dexamethasone (1 X 10(-5) or 1 X 10(-4) M) could inhibit serum-stimulated phospholipase activity in transformed 3T3 cells after 1 to 24 hr of treatment. However, no inhibition of activity was measured in palate mesenchymal cells following this period of treatment. Not until 120 hr of treatment with dexamethasone (1 X 10(-4) M) was any significant inhibition of serum-stimulated phospholipase activity observed in palate mesenchymal cells. When EGF was used to stimulate phospholipase activity, dexamethasone (1 X 10(-5) M) caused an increase in phospholipase activity in palate mesenchymal cells. These observations suggested that phospholipase in transformed 3T3 cells was sensitive to inhibition by dexamethasone. However, palate mesenchymal cell phospholipase is only minimally sensitive to dexamethasone, and in certain instances can be enhanced. These results cannot support the hypothesis that corticosteroids mediate their teratogenic effect via inhibition of phospholipase activity.

Animals↗
PubMed1992

Dexamethasone inhibition of cyclooxygenase expression in bovine term placenta.

Since both prostaglandin (PG) F2 alpha and corticosteroids are elevated in mammals before the onset of parturition, we studied the effect of the synthetic corticosteroid dexamethasone on PGF2 alpha accumulation and cyclooxygenase (prostaglandin synthase, PGS) expression in the bovine fetal placenta. Cultures were prepared from cotyledons at different stages of gestation. The effect of dexamethasone on PGF2 alpha accumulation and PGS expression was determined by radioimmunoassay and [35S]methionine metabolic labeling followed by immunoprecipitation with specific anti-cyclooxygenase antibodies, respectively. Data demonstrate that in fetal placental cells at term, both PGF2 alpha accumulation and cyclooxygenase expression are significantly inhibited after 18 hours of dexamethasone treatment (150 nM). In contrast, neither first nor second trimester cells were sensitive to dexamethasone treatment. Dexamethasone inhibition of PGF2 alpha synthesis in fetal cells at term was abolished in the presence of RNA or protein synthesis inhibitors (actinomycin D or puromycin, 10 micrograms/ml each). Neither progesterone nor 17 beta-estradiol accumulation were affected by dexamethasone treatment at any stage of gestation. Data suggest that corticosteroids play a role in parturition through PGF2 alpha synthesis regulation by fetal placental cells. Since abnormalities during parturition e.g. retained placenta, are common following dexamethasone induction of labor in cows, we postulate that the local inhibition of PGF2 alpha accumulation by cotyledon cells after corticosteroid administration, may be involved in placental retention.

Animals↗
PubMed1991

Comparison of dexamethasone and ondansetron in the prophylaxis of emesis induced by moderately emetogenic chemotherapy.

A multicentre, randomised, double-blind, cross-over trial was done to compare the efficacy and safety of a serotonin receptor antagonist--ondansetron--and dexamethasone in the prophylaxis of acute and delayed emesis and nausea induced by moderately emetogenic non-platinum-containing chemotherapy regimens. Patients were treated as outpatients and received intravenous ondansetron 4 mg or dexamethasone 8 mg before chemotherapy and oral maintenance (ondansetron 4 mg every 6 h and dexamethasone reducing from 4 mg to 1 mg 6-hourly between days 1 and 5) for 5 days. 112 patients were treated (38 men, 73 women, 1 with no gender recorded; age range 30-73 years) and 100 were evaluable for cross-over analysis. Patients taking ondansetron or dexamethasone reported no significant difference in complete and major control of acute (83% vs 79%, p = 0.46) or delayed (82% vs 88%, p = 0.214) emesis (vomiting plus retches). Significantly more patients on dexamethasone (87%) than on ondansetron (72%) reported control of delayed nausea (days 2-5) (p = 0.003). Both drugs were well tolerated with no significant difference in the number of adverse events, and this is reflected by similar patient preference for ondansetron (40%) and dexamethasone (30%) (p = 0.244). Both drugs offer adequate out-patient control of chemotherapy-induced emesis; however, dexamethasone has an advantage in the control of delayed nausea, and also in terms of cost and resource allocation.

Acute Disease↗
PubMed1984

Attempts to use thiabendazole to improve the immune response in dexamethasone-treated or stressed cattle.

Thiabendazole was evaluated in two separate experiments for its ability to enhance the immune response in dexamethasone-treated or stressed cattle. In the first experiment the cattle received either no drug treatment (controls), dexamethasone intramuscularly (IM), or dexamethasone IM plus thiabendazole orally. All animals were inoculated with heat-killed Brucella abortus strain 19, equine ferritin, tetanus toxoid, and live Corynebacterium equi at the time dexamethasone therapy was initiated. Dexamethasone (0.04 mg/kg/day IM for 3 days) significantly (p less than 0.05) inhibited the lymphocyte blastogenic response to mitogens and the antibody response to ferritin and tetanus toxoid. Thiabendazole given orally (16 mg/kg/day) beginning 24 h prior to antigen and dexamethasone administration and continued for 6 days failed to prevent the dexamethasone-induced suppression of the lymphocyte blastogenic or antibody responses. In the second experiment 51 cattle were divided into a control group and a thiabendazole-treated group. The animals were stressed by weaning, injection of antigen (equine ferritin, tetanus toxoid, B. abortus strain 19 and killed bovine viral diarrhea virus) and castration of the bulls on the day that thiabendazole therapy was started. Thiabendazole administered orally for 5 days at a dosage of 20 mg/kg did not enhance the antibody response to any of the antigens, and was associated with a significantly lower antibody response to B. abortus.

Animals↗
PubMed1984

Effects of thiabendazole on dexamethasone-induced suppression of lymphocyte and neutrophil function in cattle.

Seven dosage levels of thiabendazole were evaluated for their ability to normalize lymphocyte or neutrophil function in dexamethasone-treated cattle. Dexamethasone administration (0.04 mg/kg intramuscularly daily for 3 days) significantly suppressed the lymphocyte blastogenic response to phytohemagglutinin, concanavalin A, and pokeweed mitogen. The lymphocyte blastogenic response to allogeneic lymphocytes was also suppressed in dexamethasone-treated cattle, but this effect was not statistically significant. Neutrophils from dexamethasone-treated cattle had a significantly enhanced ability to migrate under agarose, and significantly suppressed ability to reduce nitroblue tetrazolium, iodinate protein, and mediate antibody-dependent cell-mediated cytotoxicity. Thiabendazole when administered concurrently with dexamethasone in the dosage range from 1.0 to 25.0 mg/kg (orally) did significantly enhance lymphocyte blastogenic responsiveness to phytohemagglutinin, concanavalin A, pokeweed mitogen and allogeneic cells (in dexamethasone-treated cattle). This immunonormalizing effect was not observed at the 50 or 100 mg/kg dosage levels. Thiabendazole did not produce a consistent significant enhancement of any parameter of neutrophil function in dexamethasone-treated cattle.

Animals↗
PubMedDate not supplied

Plasma dexamethasone and cortisol levels in depressed outpatients.

We investigated the 1-mg dexamethasone suppression test (DST) in 41 outpatients with major depressive disorder assessing the role of dexamethasone blood level, age and basal cortisol on DST results. Non-suppressors (approximately 25% of patients) had lower dexamethasone levels, and post-dexamethasone cortisol was negatively correlated with plasma dexamethasone; these findings were more significant after covarying out age and basal cortisol, factors that were also significantly associated to non-suppressors. A subgroup of patients (n = 19) also had 0.75-mg and 2.0-mg DST to evaluate whether a threshold dexamethasone blood level existed; a dexamethasone blood level greater than 1.5 ng/ml converted all non-suppressors to suppressors. Implications of these findings are discussed.

Adult↗
PubMed1990

An augmented escape of beta-endorphins to suppression by dexamethasone in severely depressed patients.

Baseline beta-endorphin and cortisol levels and their responses to 1 mg dexamethasone were measured in 11 healthy controls and in 35 depressed patients, categorized according to the DSM-III. Dexamethasone significantly suppressed beta-endorphin levels. Depressed patients with melancholia/psychotic features exhibited significantly increased post-dexamethasone beta-endorphin levels compared with healthy controls, minor and simple major depressives; the baseline beta-endorphin levels did not differ between those study samples. Post-dexamethasone beta-endorphin and cortisol values were found to be significantly and positively correlated. Accordingly, cortisol non-suppressors showed significantly higher post-dexamethasone beta-endorphin levels. Post-dexamethasone beta-endorphin may be the most sensitive and specific reflection of the disorder in negative feedback exerted by dexamethasone in depression.

Adult↗
PubMed1989

Dexamethasone effects on numbers of cells in lymphocyte subpopulations: changes associated with major depression and DST nonsuppression.

1. The authors studied the effects of administration of 1 mg of dexamethasone on the number of cells in discrete subpopulations of lymphocytes in major depressed and psychiatric control patients with depressive symptoms. 2. Dexamethasone significantly decreased the total lymphocyte count and numbers of T and helper T lymphocytes in control patients. 3. In contrast, dexamethasone failed to significantly decrease the numbers of cells in any of the subpopulations of lymphocytes studied in major depressed patients. 4. Among major depressed patients both DST suppressors and nonsuppressors were insensitive to the suppressive effects of dexamethasone on lymphocyte numbers. 5. However, in DST nonsuppressors, but not in DST suppressors, dexamethasone administration significantly increased the number of cytotoxic/suppressor T lymphocytes and natural killer cells. 6. The authors conclude that insensitivity to the suppressive effects of dexamethasone on lymphocyte numbers is specific to major depression and is not associated with DST status. However, DST nonsuppression is associated with a facilitating effect of dexamethasone on the number of cells in some subpopulations of lymphocytes.

Adolescent↗
PubMed1987

Inhibitory and stimulatory effects of dexamethasone and 1,25-dihydroxyvitamin D3 on chick intestinal calbindin-D28K and its mRNA.

The present study examined the interactions of the synthetic glucocorticoid, dexamethasone, with the regulation of chick intestinal calbindin-D28K (a 28,000 Da vitamin D-dependent calcium binding protein, CaBP) and its mRNA by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). Dexamethasone (0-500 nmol) had a neutral impact on calbindin levels in the rachitic chick intestine when measured 12 h later. However, dexamethasone appeared to exert a significant, though modest, stimulatory influence upon calbindin-mRNA accumulation in the vitamin D-deficient (-D) intestine when measured 12 h after administration. 1,25(OH)2D3 also stimulated calbindin-mRNA accumulation in the -D chick intestine; half-maximal (ED50) doses were 1.1 nmol (7.6-fold) and 12.6 nmol (4.3-fold stimulation) for 1,25(OH)2D3 and dexamethasone respectively. In contrast, when both 1,25(OH)2D3 and dexamethasone were administered simultaneously, the stimulatory effect of 1,25(OH)2D3 (and that of the glucocorticoid) was lost in terms of calbindin and calbindin-mRNA accumulation. Dexamethasone treatment of vitamin D-replete (+D) chicks resulted in a depression of calbindin-mRNA accumulation; levels were depressed to baseline with 250 nmol/bird. Dexamethasone (1.25 mumol per day for 3 days) also induced an apparent 'down-regulation' of the 1,25(OH)2D3 receptor population in the -D chick intestine but failed to influence the binding of 1,25(OH)2D3 to its receptor in vitro. Taken collectively, these data indicate that glucocorticoids are able to influence the receptor-mediated action of 1,25(OH)2D3, possibly at the level of calbindin-D28K gene expression.

Animals↗
PubMed1981

Binding of dexamethasone and inhibition of transport of 3-O-methylglucose in rat thymocytes.

The effect of temperature (21-37 degrees C) on binding of [3H]dexamethasone in intact rat thymocytes was investigated. Receptor binding was correlated with inhibition by dexamethasone of in vitro transport of 3-O-[14C]methyl-D-glucose at 37 degrees C. Receptor binding of dexamethasone was dependent on temperature. The number of receptors per cell was about 3000 at all temperatures studied. However, an increase of temperature from 21 to 37 degrees C changed the rate constant of dissociation from 6.0 . 10(-3) min-1 to 55.0 . 10(-3) min-1, and the dissociation constant from 1.1 to 5.9 nM. The effect of dexamethasone (0.8-790 nM) on transport of 3-O-[14C]-methyl-D-glucose (10-50 muM) was investigated during the initial 30 s of uptake at 37 degrees C. A dose-dependent inhibition of transport was found at 60 and 120 min after the addition of hormone. Correlation between effect and receptor occupancy was linear. Maximal inhibition was achieved at concentrations of dexamethasone resulting in 95-97% receptor occupancy, and 50% of the maximal effect was obtained at a concentration of dexamethasone corresponding to 50% receptor occupancy. Inhibition of transport differed in latency between cell preparations. However, this could not be ascribed to change of either amount of affinity of dexamethasone receptors.

Animals↗
PubMed1983

Dexamethasone-sensitive and -insensitive responses during in vitro differentiation of Friend erythroleukemia cells.

We have investigated the mechanism(s) by which dexamethasone inhibit DMSO-induced Friend erythroleukemia cell differentiation in vitro. In particular, we examined the effects of dexamethasone on (a) the early events of differentiation such as cell volume alterations and 'memory response' and (b) the onset of biochemical events associated with terminal erythroid cell differentiation. By analysing kinetics of commitment of Friend cells to terminal erythroid differentiation on a clonal basis, we have observed that dexamethasone inhibited the completion of the latent period (time elapsed prior to commitment) and impaired "memory" (ability to inducer-treated cells to continue differentiation after a discontinuous exposure to inducer). Treatment of Friend cells with dexamethasone did not prevent the occurrence of DMSO-induced alterations in cell volume. However, dexamethasone treatment prevented a series of biochemical events associated with terminal Friend cell differentiation. These include the decrease in the rate of both cytoplasmic and nuclear RNA synthesis as well as the induction of cytidine deaminase activity and hemoglobin synthesis. These data indicate that the dexamethasone-sensitive process(es) operate during the early stages of Friend cell differentiation and that they are responsible for the inhibition of terminal erythroid maturation. These dexamethasone-sensitive processes, however, appear to be different from those regulating cell volume alterations during the early steps of DMSO-induced Friend cell differentiation.

Animals↗
PubMed1985

Pre- and post-dexamethasone salivary cortisol concentrations in major depression.

Seventy patients fulfilling DSM-III criteria for major depression were given the 1.0 mg overnight dexamethasone suppression test, with salivary cortisol concentrations being measured as the dependent variable. Using both the DSM-III and the Research Diagnostic Criteria, we categorized the patients into four groups based on increasing frequency of endogenous symptomatology. Among these four groups there were no significant differences in salivary cortisol concentrations either before dexamethasone or eight, 16, and 24 h after dexamethasone. Similarly, there were no significant differences among the groups in either the ratios of post- to pre-dexamethasone salivary cortisol or the frequencies of positive tests based on several criterion levels of cortisol for the three post-dexamethasone samples. Multiple regression analyses indicated that the Hamilton depression rating scale item "somatic anxiety" was significantly negatively related to post-dexamethasone cortisol concentrations. We conclude that, for our sample of major depressives, the salivary cortisol dexamethasone suppression test showed no utility as a laboratory correlate of depressive episodes with endogenous features.

Adult↗
PubMed1984

Modification by dexamethasone of radiation response of in vitro cultured cells.

Because of the potential clinical significance of the report that dexamethasone is a radioprotector of Chinese hamster V-79 cells, the effect of dexamethasone treatment on the radiosensitivity of five other cultured mammalian cell lines (including two human cell lines) was tested and preliminary investigations into the mechanism of protection of V-79 cells were undertaken. In agreement with the published results of others, we found that treatment of V-79 cells with dexamethasone results in a 1.3-fold increase in D0. Conversely, dexamethasone had no effect on the radiosensitivity of Chinese hamster ovary cells, murine fibrosarcoma, rat glioma cells, human diploid fibroblasts, or human mammary carcinoma cells. To study the mechanism of the radioprotective effect of dexamethasone on V-79 cells, the cell cycle was examined. Dexamethasone treatment causes a change in cell cycle distribution in V-79 cells, resulting in a dose-dependent reduced fraction of S-phase and an increased fraction of G1- and G2 + M-phase cells. However, these kinetic changes cannot explain the observed radioprotection of asynchronous populations, since purified G1 cells are more radiosensitive. Furthermore, cells synchronized in G1 by centrifugal elutriation were shown to be protected by dexamethasone to the same extent as was the unsorted population, thereby ruling out the mechanism of protection being a redistribution in the cell cycle.

Animals↗
PubMed1993

The effect of starting time on dexamethasone suppression test results in horses.

This study was conducted to investigate the effect of starting time on dexamethasone suppression test results in horses. Eight adult horses were used throughout the trial. Baseline cortisol levels were established by collecting cortisol levels twice daily, at 8:00 A.M. and 8:00 P.M. for 4 consecutive days. Morning baseline cortisol levels were 46.3 +/- 5.94 ng/ml, and evening baseline cortisol levels were 32.8 +/- 5.59 ng/ml. Although lower, the evening cortisol levels were not statistically different (P = 0.154) from the morning levels. Dexamethasone suppression tests initiated at either 9:00 A.M. or 9:00 P.M. were performed by collected a control blood sample, administering either 0.044 mg/kg dexamethasone or its vehicle intravenously and then collecting additional blood samples at 6, 12, 24, 36, and 48 hr after treatment. Mean cortisol levels at hr 0, 6, 12, 24, 36, and 48 after a dexamethasone injection given at 9:00 A.M. were 55.6 +/- 3.08, 6.4 +/- 2.05, 0.73 +/- 0.48, 11.0 +/- 5.82, 12.6 +/- 4.30, and 40.5 +/- 5.38 ng/ml respectively. Mean cortisol levels at hr 0, 6, 12, 24, 36, and 48 hr after a dexamethasone injection given at 9:00 P.M. were 45.0 +/- 6.03, 4.5 +/- 1.28, 0.20 +/- 0.12, 4.5 +/- 2.49, 23.4 +/- 5.88, and 29.5 +/- 6.61 ng/ml respectively. There was no statistical difference in cortisol values between A.M. and P.M. initiated tests at any hour post dexamethasone administration. There was no decrease in cortisol level after administration of dexamethasone vehicle.

Analysis of Variance↗
PubMed1994

Efficacy and tolerability of tropisetron in comparison with a combination of tropisetron and dexamethasone in the control of nausea and vomiting induced by cisplatin-containing chemotherapy.

In a double-blind, randomised, multicentre study, the efficacy and tolerability of tropisetron and a combination of tropisetron and dexamethasone were compared for the control of nausea and vomiting induced by cisplatin in patients previously not entirely protected by tropisetron monotherapy. In all, 160 women with gynaecological cancers were studied during two consecutive courses of cisplatin-containing chemotherapy. During the first course (the screening course), all patients received tropisetron monotherapy [5 mg intravenous (i.v.) on day 1 and 5 mg orally on days 2-6] as antiemetic treatment. During the second course (the test course), tropisetron was compared with a combination of tropisetron and dexamethasone (20 mg i.v. on day 1 and 4.5 mg twice daily on days 2-6). This part of the study was double-blind, randomised and placebo-controlled. Candidates for randomisation were patients with partial control of nausea (< 12 h of nausea) or partial control of vomiting (1-4 episodes of vomiting) during the screening course. Patients with complete control of nausea and vomiting in the screening course continued with tropisetron monotherapy; patients with treatment failure received open rescue treatment in course 2. Total control of acute nausea was achieved in 37% of the tropisetron + placebo group and in 75% of the tropisetron + dexamethasone group (P = 0.001). Significantly more patients on tropisetron-dexamethasone than on tropisetron-placebo were also free of delayed nausea. Acute vomiting was prevented in 40% of the patients in the placebo group and in 75% in the dexamethasone group (P = 0.001). Delayed vomiting was also significantly less frequent in dexamethasone-treated patients than in placebo-treated patients. Tropisetron was well tolerated both as monotherapy and in combination with dexamethasone. The most frequent adverse events were headache (34%), constipation (12.5%) and fatigue (12.5%). Adding high doses of a corticosteroid did not induce further adverse events or disregulate concurrent diseases.

Adult↗
PubMed2005

Dexamethasone-induced methylprednisolone hemisuccinate hydrolase: its identification as a member of the rat carboxylesterase 2 family and its unique existence in plasma.

Carboxylesterases (CESs) play important roles in the metabolism of many ester-drugs. In the present study, we identified and characterized dexamethasone-induced methylprednisolone hemisuccinate (MPHS) hydrolase in rat liver microsomes. Intraperitoneal injection of dexamethasone resulted in a significant increase in the level of MPHS hydrolase activity accompanied by induction of a specific CES isozyme. Since the biochemical characteristics of the induced CES isozyme were very similar to those of rat CES RL4, we hypothesized that these were the same enzymes. The results of nano-electrospray ionization tandem mass spectrometry analysis revealed that both dexamethasone-induced CES isozyme and CES RL4 possessed identical peptide fragments to those of , a rat CES2 isozyme, supporting our hypothesis. Furthermore, the results of reverse transcription-polymerase chain reaction showed that the amount of mRNA in dexamethasone-treated liver was greater than that in control liver. To confirm that encodes dexamethasone-induced CES isozyme, cDNA cloning was performed and the obtained cDNA was expressed in Sf9 cells by using a baculovirus-mediated expression system. The recombinant CES protein could hydrolyze MPHS and exhibited biochemical characteristics similar to those of CES RL4. Collectively, the results indicated that dexamethasone-induced MPHS hydrolase in liver microsomes is a rat CES2 isozyme. Interestingly, the results also showed that this rat CES2 isozyme exists in plasma and that the amount of this protein is increased by dexamethasone. These findings, together with the findings described above, provide important information for the study of phramacokinetics and pharmacodynamics of ester-drugs as well as for the study of CESs.

Amino Acid Sequence↗