Inhibition of aromatase activity in rat Sertoli cells by thyroid hormone

1994 ◽  
Vol 140 (3) ◽  
pp. 431-436 ◽  
Author(s):  
S Ulisse ◽  
E A Jannini ◽  
E Carosa ◽  
D Piersanti ◽  
F M Graziano ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Cyclic Amp ◽  
Sertoli Cells ◽  
Inhibitory Effect ◽  
Aromatase Activity ◽  
Dependent Manner ◽  
Maximal Dose ◽  
Cyclic Amp Accumulation ◽  
Order Of Magnitude ◽  
Dose Dependent

Abstract Basal and FSH-induced aromatase activity in prepubertal rat Sertoli cells was inhibited by l-tri-iodothyronine (T3) in a time- and dose-dependent manner. The effect was evident only after 6 h of preincubation with T3 (10−7 m) and the half-maximal dose was 0·5 ±0·2 nm, which correlated with the Kd of the nuclear T3 receptor of rat Sertoli cells (Kd=1–2 nm). The effect was specific as judged by the lack of effect of the T3 analogue 3-iodo-l-thyrosine. The inhibitory effect of T3 was present over the entire range of FSH concentrations used (0·001–100 ng/ml). In T3-treated Sertoli cells, aromatase activity induced by 8-bromo-cyclic AMP was inhibited by the same order of magnitude as that of FSH, thus suggesting that the inhibitory effect of T3 was downstream from cyclic AMP formation. Furthermore, pretreatment of Sertoli cells cultures with T3 (24 h, 10−7 m) did not affect basal or FSH-induced extracellular cyclic AMP accumulation. This effect of T3 on rat Sertoli cell aromatase activity may be regarded as a part of the integrated mechanism by which thyroid hormone modulates the functions of the seminiferous epithelium. Journal of Endocrinology (1994) 140, 431–436

Inhibitory effect of neurohypophysial peptides on cyclic AMP accumulation by isolated hepatocytes of the trout

1988 ◽  
Vol 119 (3) ◽  
pp. 439-445 ◽  
Author(s):  
B. Lahlou ◽  
B. Fossat ◽  
J. Porthé-Nibelle ◽  
L. Bianchini ◽  
M. Guibbolini
Keyword(s):  
Rainbow Trout ◽  
Cyclic Amp ◽  
Isolated Hepatocytes ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Half Maximum ◽  
Cyclic Amp Accumulation ◽  
High Concentrations ◽  
Dose Dependent ◽  
Glucagon Concentration

ABSTRACT Cyclic AMP levels were measured in freshly isolated hepatocytes of the rainbow trout. Compared with basal values, the average levels were increased up to 60 times in a dose-dependent manner either by mammalian glucagon (concentration range 1 nmol– 1 μmol/l; dose giving half maximum response (EC50) 0· 18 μmol/l) or by forskolin (concentration range 0·1–100 μmol/l; EC50 about 10 μmol/l). These stimulatory effects were partially inhibited by fish or mammalian neurohypophysial hormones used at relatively high concentrations (1–5 μmol/l). It is suggested that these results are evidence for the presence of V1-type receptors in fish hepatocytes. Together with previous results obtained with gills on the hormonal inhibition of adenylate cyclase activity, they suggest that teleost fish may possess only V1-type receptors (or two V1-related types), while the V2 receptors have evolved (or have become functional) in higher vertebrates. J. Endocr. (1988) 119, 439–445

scholarly journals Cross-talk between glucagon- and adenosine-mediated signalling systems in rat hepatocytes: effects on cyclic AMP-phosphodiesterase activity

1995 ◽  
Vol 312 (3) ◽  
pp. 763-767 ◽  
Author(s):  
M Robles-Flores ◽  
G Allende ◽  
E Piña ◽  
J A García-Sáinz
Keyword(s):  
Cyclic Amp ◽  
Pertussis Toxin ◽  
Plasma Membranes ◽  
Rat Hepatocytes ◽  
Dependent Manner ◽  
Phosphodiesterase Activity ◽  
Cyclic Amp Phosphodiesterase ◽  
Cyclic Amp Accumulation ◽  
A1 Adenosine Receptors ◽  
Dose Dependent

The effect of adenosine analogues on glucagon-stimulated cyclic AMP accumulation in rat hepatocytes was explored. N6-Cyclopentyladenosine (CPA), 5′-N-ethylcarboxamidoadenosine and N6-(R-phenylisopropyl)adenosine inhibited in a dose-dependent manner the cyclic AMP accumulation induced by glucagon. This effect seems to be mediated through A1 adenosine receptors. Pertussis toxin completely abolished the effect of CPA on glucagon-stimulated cyclic AMP accumulation in whole cells which suggested that a pertussis-toxin-sensitive G-protein was involved. On the other hand, this action of adenosine analogues on glucagon-induced cyclic AMP accumulation was reverted by the selective low-Km cyclic AMP-phosphodiesterase inhibitor Ro 20-1724. Analysis of cyclic AMP-phosphodiesterase activity in purified hepatocyte plasma membranes showed that glucagon in the presence of GTP inhibited basal PDE activity by 45% and that CPA reverted this inhibition in dose-dependent manner. In membranes derived from pertussis-toxin-treated rats, we observed no inhibition of cyclic AMP-phosphodiesterase activity by glucagon in the absence or presence of CPA. Our results indicate that in hepatocyte plasma membranes, stimulation of adenylate cyclase activity and inhibition of a low-Km cyclic AMP phosphodiesterase activity are co-ordinately regulated by glucagon, and that A1 adenosine receptors can inhibit glucagon-stimulated cyclic AMP accumulation by blocking glucagon's effect on phosphodiesterase activity.

scholarly journals Changes in adenosine receptors during differentiation of 3T3-F442A cells to adipocytes

1988 ◽  
Vol 249 (2) ◽  
pp. 377-381 ◽  
Author(s):  
K Ravid ◽  
J M Lowenstein
Keyword(s):  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Adenosine Receptors ◽  
Positive Response ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Similar Extent ◽  
Phenylisopropyl Adenosine ◽  
Dose Dependent ◽  
Basal Concentration

Incubation of undifferentiated 3T3-F442A cells (preadipocytes) with 5′-N-ethylcarboxamidoadenosine (NECA) increases intracellular cyclic AMP in a dose-dependent manner. The effect of NECA is antagonized by 8-phenyltheophylline, but potentiated by 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidine, an inhibitor of cyclic AMP phosphodiesterase. Incubation of preadipocytes with (-)-N6-(R-phenylisopropyl)adenosine (PIA) has no inhibitory effect on the basal concentration of cyclic AMP or on the stimulation of adenylate cyclase by isoprenaline or forskolin. Micromolar concentrations of PIA increase intracellular cyclic AMP, but with a lower potency than NECA. Similar findings are obtained with the non-differentiating cell line 3T3-C2. Thus preadipocyte 3T3-F442A cells and 3T3-C2 cells appear to express only stimulatory adenosine receptors. For some time after 3T3-F442A cells have differentiated to adipocytes, micromolar concentrations of NECA and PIA continue to increase cyclic AMP to a similar extent to that in preadipocytes, whereas nanomolar concentrations of PIA decrease the stimulatory effects of isoprenaline and forskolin on adenylate cyclase by 50%. However, several days after differentiation, the adipocytes gradually lose the major part of their positive response to NECA and reach a steady response to NECA 10 days after differentiation. The inhibition of adenylate cyclase caused by PIA remains constant for at least 2 weeks after differentiation. With membranes derived from the cells, the effects of NECA and PIA depend on GTP. These results indicate that, during the differentiation of 3T3-F442A cells to adipocytes, new inhibitory adenosine receptors are expressed, whereas the stimulatory receptors become attenuated.

scholarly journals Use of forskolin to study the relationship between cyclic AMP formation and bone resorption in vitro

1986 ◽  
Vol 240 (2) ◽  
pp. 529-539 ◽  
Author(s):  
U H Lerner ◽  
B B Fredholm ◽  
M Ransjö
Keyword(s):  
Bone Resorption ◽  
Cyclic Amp ◽  
Phosphodiesterase Inhibitor ◽  
Inhibitory Effect ◽  
Cyclic Amp Accumulation ◽  
The Relationship ◽  
Dose Dependent ◽  
Old Mice ◽  
45Ca Release

The effect of the adenylate cyclase activator forskolin on bone resorption and cyclic AMP accumulation was studied in an organ-culture system by using calvarial bones from 6-7-day-old mice. Forskolin caused a rapid and fully reversible increase of cyclic AMP, which was maximal after 20-30 min. The phosphodiesterase inhibitor rolipram (30 mumol/l), enhanced the cyclic AMP response to forskolin (50 mumol/l) from a net cyclic AMP response of 1234 +/- 154 pmol/bone to 2854 +/- 193 pmol/bone (mean +/- S.E.M., n = 4). The cyclic AMP level in bones treated with forskolin (30 mumol/l) was significantly increased after 24 h of culture. Forskolin, at and above 0.3 mumol/l, in the absence and the presence of rolipram (30 mumol/l), caused a dose-dependent cyclic AMP accumulation with an calculated EC50 (concentration producing half-maximal stimulation) value at 8.3 mumol/l. In 24 h cultures forskolin inhibited spontaneous and PTH (parathyroid hormone)-stimulated 45Ca release with calculated IC50 (concentration producing half-maximal inhibition) values at 1.6 and 0.6 mumol/l respectively. Forskolin significantly inhibited the release of 3H from [3H]proline-labelled bones stimulated by PTH (10 nmol/l). The inhibitory effect by forskolin on PTH-stimulated 45Ca release was significant already after 3 h of culture. In 24 h cultures forskolin (3 mumol/l) significantly inhibited 45Ca release also from bones stimulated by prostaglandin E2 (1 mumol/l) and 1 alpha-hydroxycholecalciferol (0.1 mumol/l). The inhibitory effect of forskolin on spontaneous and PTH-stimulated 45Ca release was transient. A dose-dependent stimulation of basal 45Ca release was seen in 120 h cultures, at and above 3 nmol of forskolin/l, with a calculated EC50 value at 16 nmol/l. The stimulatory effect of forskolin (1 mumol/l) could be inhibited by calcitonin (0.1 unit/ml), but was insensitive to indomethacin (1 mumol/l). Forskolin increased the release of 3H from [3H]proline-labelled bones cultured for 120 h and decreased the amount of hydroxyproline in bones after culture. Forskolin inhibited PTH-stimulated release of Ca2+, Pi, beta-glucuronidase and beta-N-acetylglucosaminidase in 24 h cultures. In 120 h cultures forskolin stimulated the basal release of minerals and lysosomal enzymes.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Effects of verapamil on lipolysis due to dibutyryl cyclic AMP

1984 ◽  
Vol 220 (1) ◽  
pp. 321-324 ◽  
Author(s):  
H Goko ◽  
S Takashima ◽  
S Shimizu ◽  
S Kagawa ◽  
A Matsuoka
Keyword(s):  
Cyclic Amp ◽  
Adrenergic Receptors ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Dibutyryl Cyclic Amp ◽  
Alpha Adrenergic Receptors ◽  
Biphasic Effect ◽  
Adrenergic Antagonists ◽  
Dose Dependent ◽  
Isolated Rat

The effects of verapamil, a calcium antagonist, on lipolysis in isolated rat adipocytes were studied. Verapamil (100 microM) potentiated lipolysis due to dibutyryl cyclic AMP (Bt2cAMP) at submaximal concentrations, with or without extracellular Ca2+. Lipolysis due to 0.5 mM-Bt2cAMP was potentiated by verapamil in a dose-dependent manner up to 200 microM, whereas at concentrations higher than 100 microM the stimulatory effect of verapamil was progressively diminished with or without extracellular Ca2+. Verapamil showed only an inhibitory effect on lipolysis due to adrenaline (0.1-10 microM) or 3-isobutyl-1-methylxanthine (IBMX; 25-200 microM). The stimulatory effect of verapamil on lipolysis due to Bt2cAMP was not blocked by alpha-adrenergic antagonists. These results suggest (i) that verapamil has a biphasic effect on lipolysis due to Bt2cAMP and only an inhibitory effect on that due to adrenaline or IBMX, and (ii) that extracellular Ca2+ or alpha-adrenergic receptors are not involved in the action of verapamil.

Ganglioside inhibition of attachment and differentiation of cultured rat granulosa cells: interactions with fibronectin

1987 ◽  
Vol 88 (2) ◽  
pp. 205-217
Author(s):  
P. Morley ◽  
D.T. Armstrong ◽  
R.E. Gore-Langton
Keyword(s):  
Cyclic Amp ◽  
Granulosa Cells ◽  
Cell Attachment ◽  
Inhibitory Effect ◽  
Defined Medium ◽  
Cellular Protein ◽  
Aromatase Activity ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Cellular Protein Content

The involvement of fibronectin in the attachment and differentiation of rat granulosa cells, cultured in a chemically defined medium, was investigated using the inhibitory properties of mixed brain gangliosides (MBGs) and highly purified disialoganglioside, GD1a. MBGs inhibited cell attachment to plastic culture surfaces in a concentration-dependent manner, with 0.1 mmol l-1 causing significantly decreased attachment between 0.5 and 24 h of incubation. Inhibition of attachment to a fibronectin-coated substratum was even greater. The inhibitory effect of MBGs was not caused by binding to the cell surface, but instead the inhibitory factor(s) were adsorbed on a surface of immobilized human plasma fibronectin, thereby preventing cell attachment to this surface. The inhibitory action of MBGs was also neutralized by the addition of soluble fibronectin. Furthermore, at least one component of MBGs, detected chemically following thin-layer chromatography, was directly shown to bind to human fibronectin. MBGs inhibited to varying degrees the follicle-stimulating hormone(FSH)-dependent responses: augmentation of cellular protein content, production of adenosine 3′,5′-cyclic monophosphate (cyclic AMP) and progestins (progesterone + 20 alpha-hydroxypregn-4-en-3-one + pregnenolone), and induction of aromatase activity. These inhibitory activities of MBGs could not be eliminated by adsorption on immobilized fibronectin or reversed by addition of soluble fibronectin, thus distinguishing these actions from the early inhibition of cell attachment. FSH-dependent responses were also inhibited by GD1a, while responses to stimulation by dibutyryl cyclic AMP plus 3-isobutyl-1-methyl xanthine were less affected by this ganglioside. These results suggest that gangliosides inhibit attachment of granulosa cells in culture by binding to fibronectin, whereas the inhibition of FSH-dependent differentiation occurs by other modes of action that are unrelated to the effects on cell adhesion.

GnRH ACTION IN RAT ANTERIOR PITUITARY GLAND: REGULATION OF PROTEIN, GLYCOPROTEIN AND LH SYNTHESIS

1977 ◽  
Vol 86 (3) ◽  
pp. 473-488 ◽  
Author(s):  
K. M. J. Menon ◽  
K. P. Gunaga ◽  
S. Azhar
Keyword(s):  
Cyclic Amp ◽  
Anterior Pituitary ◽  
Amino Acid Mixture ◽  
Acid Mixture ◽  
Dependent Manner ◽  
Dibutyryl Cyclic Amp ◽  
Concomitant Increase ◽  
Cyclic Amp Accumulation ◽  
Dose Dependent

ABSTRACT The effect of synthetic GnRH on the synthesis of proteins and glycoproteins in the anterior pituitary and in vitro release of LH into the medium was studied. A maximal dose (25 ng/ml) of synthetic GnRH caused optimum release of radioimmunoassayable LH into the medium after 2 h of incubation. A concomitant increase in cyclic AMP accumulation in the tissue and LH in the incubation medium was also observed under the influence of GnRH during different periods of incubation time. Incubation of the rat anterior pituitary with GnRH stimulated the incorporation of [3H]proline into acid precipitable proteins in a time- and dose-dependent manner, similar to radioimmunoassayable LH released into the medium. Similar results were obtained when pituitary was incubated with dibutyryl cyclic AMP. LH, in addition, enhanced the incorporation of [3H]glucosamine and [3H]amine acids mixture into acidprecipitable proteins suggesting that proteins including glycoproteins are synthesized by the rat anterior pituitary under the influence of GnRH. Approximately 10 % of the radioactivity associated with proteins comigrated with radioimmunoassayable LH on the gels. GnRH also enhanced the incorporation of [3H]glucosamine and [3H]amino acid mixture into immunoprecipitable LH. The GnRH-induced incorporation of [3H]proline into anterior pituitary proteins was abolished by specific translation inhibitors.

Synthesis and Assessment of Novel Anti-chlamydial Benzylidene Acylhydrazides Derivatives

2018 ◽  
Vol 15 (1) ◽  
pp. 31-36 ◽  
Author(s):  
Xiaofeng Bao ◽  
Ying Xue ◽  
Chao Xia ◽  
Yin Lu ◽  
Ningjing Yang ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Dependent Manner ◽  
Iron Starvation ◽  
Hydrochloride Salt ◽  
Obligate Intracellular ◽  
Biphasic Life Cycle ◽  
Ic50 Value ◽  
Ic50 Values ◽  
Dose Dependent ◽  
Better Than

Background: Chlamydiae, characterized by a unique biphasic life cycle, are a group of Gram-negative obligate intracellular bacterial pathogens responsible for diseases in a range of hosts including humans. Benzylidene acylhydrazide CF0001 could inhibit chlamydiae independent of iron starvation and T3SS inhibition. This finding promoted us to design and synthesize more benzylidene acylhydrazides to find novel anti-chlamydial agents. Methods: The carboxylic acids 1a-1d were coupled with Boc-hydrazide inpresence of EDCI and DMAP to obtain the intermediate 2a-2d in 60-62% yields. N-Boc deprotections were performed to obtain hydrazide hydrochloride salt 3a-3d. Nextly, the hydrazides were subjected to condensation with aldehydes to obtain benzylidene acylhydrazides 4a-4g in 30-52% yields in two steps. Results: Compound 4d exhibited best inhibitory effect on the formation and growth of chlamydial inclusions. The IC50 value of compound 4d for infectious progenies was 3.55 µM, better than 7.30 µM of CF0001. Conclusion: To find novel anti-chlamydial agents, we have designed and synthesized benzylidene acylhydrazides 4a-4g. Compounds 4a, 4d, 4g showed inhibitory activity on C. muridarum with the IC50 values from 3.55-12 µM. The 3,5-dibromo-4-hydroxyl substitutes on ring B are critical to keep their anti-chlamydial activity. Compound 4d inhibited C. muridarum in a dose-dependent manner without apparent cytotoxicity.

scholarly journals In vitro study on the effect of cornin on the activity of cytochrome P450 enzymes

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qun Zhang ◽  
Zengqiang Qu ◽  
Yanqing Zhou ◽  
Jin Zhou ◽  
Junwei Yang ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Drug Interaction ◽  
Liver Microsomes ◽  
In Vitro Study ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Cytochrome P450 Enzymes ◽  
Drug Drug Interaction ◽  
Dose Dependent

Abstract Background Cornin is a commonly used herb in cardiology for its cardioprotective effect. The effect of herbs on the activity of cytochrome P450 enzymes (CYP450s) can induce adverse drug-drug interaction even treatment failure. Therefore, it is necessary to investigate the effect of cornin on the activity of CYP450s, which can provide more guidance for the clinical application of cornin. Methods Cornin (100 μM) was incubated with eight isoforms of CYP450s, including CYP1A2, 2A6, 3A4, 2C8, 2C9, 2C19, 2D6, and 2E1, in pooled human liver microsomes. The inhibition model and corresponding parameters were also investigated. Results Cornin exerted significant inhibitory effect on the activity of CYP3A4, 2C9, and 2E1 in a dose-dependent manner with the IC50 values of 9.20, 22.91, and 14.28 μM, respectively (p < 0.05). Cornin inhibited the activity of CYP3A4 non-competitively with the Ki value of 4.69 μM, while the inhibition of CYP2C9 and 2E1 by cornin was competitive with the Ki value of 11.31 and 6.54 μM, respectively. Additionally, the inhibition of CYP3A4 by cornin was found to be time-dependent with the KI/Kinact value of 6.40/0.055 min− 1·μM− 1. Conclusions The inhibitory effect of cornin on the activity of CYP3A4, 2C9, and 2E1 indicated the potential drug-drug interaction between cornin and drugs metabolized by these CYP450s, which needs further investigation and validation.

Immunomodulatory activities of whey fractions in efferent prefemoral lymph of sheep

1996 ◽  
Vol 63 (2) ◽  
pp. 257-267 ◽  
Author(s):  
Chun W. Wong ◽  
Geoffrey O. Regester ◽  
Geoffrey L. Francis ◽  
Dennis L. Watson
Keyword(s):  
Immune Responses ◽  
Bovine Milk ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Milk Whey ◽  
Significant Difference ◽  
Lymphocyte Phenotypes ◽  
Dose Dependent

SummaryStudies on the immunomodulatory activities of ruminant milk and colostral whey fractions were undertaken. By comparing with boiled colostral whey in a preliminary experiment, a putative heat-labile immunostimulatory factor for antibody responses was found to be present in ovine colostral whey. Studies were then undertaken in sheep in which the efferent prefemoral lymphatic ducts were cannulated bilaterally, and immune responses in the node were measured following subcutaneous injection in the flank fold of whey protein preparations of various purities. A significant sustained decline of efferent lymphocyte output was observed following injection with autologous crude milk whey or colostral whey preparations, but no changes were observed in interferon-gamma levels in lymph plasma. Two bovine milk whey fractions (lactoperoxidase and lactoferrin) of high purity were compared in bilaterally cannulated sheep. A transient decline over the first 6 h was seen in the efferent lymphocyte output and lymph flow rate after injection of both fractions. A significant difference was seen between the two fractions in interferongamma levels in lymph at 6 h after injection. However, no significant changes in the proportion of the various efferent lymphocyte phenotypes were seen following either treatment. Whereas both fractions showed a significant inhibitory effect in a dose-dependent manner on the proliferative response of T lymphocytes, but not B lymphocytes, to mitogenic stimulation in vitro, no similar changes were seen following in vivo stimulation with these two fractions.

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