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.

scholarly journals Calcium rather than cyclic AMP is an intracellular messenger of parathyroid hormone action on glycogen metabolism in isolated rat hepatocytes

1989 ◽  
Vol 258 (3) ◽  
pp. 889-894 ◽  
Author(s):  
T Mine ◽  
I Kojima ◽  
E Ogata
Keyword(s):  
Parathyroid Hormone ◽  
Cyclic Amp ◽  
Glucose Production ◽  
Rat Hepatocytes ◽  
Free Calcium ◽  
Dependent Manner ◽  
Isolated Rat Hepatocytes ◽  
Glucose Output ◽  
Dose Dependent ◽  
Isolated Rat

The synthetic 1-34 fragment of human parathyroid hormone (1-34hPTH) stimulated glucose production in isolated rat hepatocytes. The effect of 1-34hPTH was dose-dependent and 10(10) M-1-34 hPTH elicited the maximum glucose output, which was approx. 80% of that by glucagon. Although 1-34hPTH induced a small increase in cyclic AMP production at concentrations higher than 10(-9) M, 10(-10) M-1-34hPTH induced the maximum glucose output without significant elevation of cyclic AMP. This is in contrast to the action of forskolin, which increased glucose output to the same extent as 10(-10) M-1-34hPTH by causing a 2-fold elevation of cyclic AMP. In addition to increasing cyclic AMP, 1-34hPTH caused an increase in cytoplasmic free calcium concentration ([Ca2+]c). When the effect of 1-34hPTH on [Ca2+]c was studied in aequorin-loaded cells, low concentrations of 1-34hPTH increased [Ca2+]c: the 1-34hPTH effect on [Ca2+]c was detected at as low as 10(-12) M and increased in a dose-dependent manner. 1-34hPTH increased [Ca2+]c even in the presence of 1 microM extracellular calcium, suggesting that PTH mobilizes calcium from an intracellular pool. In line with these observations, 1-34hPTH increased the production of inositol trisphosphate. These results suggest that: (1) PTH activates both cyclic AMP and calcium messenger systems and (2) PTH stimulates glycogenolysis mainly via the calcium messenger system.

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.

Theophylline Inhibition of Nucleoside Transport and its Relation to Cyclic AMP in Skeletal Muscle

1974 ◽  
Vol 52 (6) ◽  
pp. 1063-1073 ◽  
Author(s):  
Yin-Tak Woo ◽  
J. F. Manery ◽  
E. E. Dryden
Keyword(s):  
Skeletal Muscle ◽  
Cyclic Amp ◽  
Phosphodiesterase Inhibitor ◽  
Inhibitory Effect ◽  
Nucleoside Transport ◽  
Intracellular Uptake ◽  
Frog Skeletal Muscle ◽  
Dibutyryl Cyclic Amp ◽  
Cyclic Amp Phosphodiesterase ◽  
Dose Dependent

Using [14C]inosine and [3H]sorbitol, the effect of theophylline on inosine uptake was studied. Theophylline inhibited the intracellular uptake of inosine by isolated, frog skeletal muscle in a dose-dependent way. An inhibitory effect was also observed for the uptake of labelled adenosine, uridine, hypoxanthine, and adenine, but not for ribose. The inhibition was not readily reversible and was noncompetitive in nature. It was not secondary to the contracture of the muscle produced by the drug, because various treatments known to cause contracture had no effect on inosine transport. Also, papaverine (0.3 mM) significantly inhibited inosine transport without affecting the contractile properties of the muscle. Although theophylline is a cyclic AMP phosphodiesterase inhibitor, no relation could be found between inhibition of inosine uptake and cyclic AMP. N8,O2′-Dibutyryl cyclic AMP (1 mM) was ineffective. Though isoproterenol (10 μg/ml) increased the cyclic AMP concentrations in the muscle by 26-fold in the presence of theophylline and 3-fold in the absence of the drug, it did not influence inosine transport. Tracing the label into various intracellular nucleotides after incubation of the muscle with [14C]inosine suggested that theophylline inhibited inosine transport rather than inosine metabolism.

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

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.

scholarly journals The action of local anaesthetics on lipolysis and on adenosine 3′:5′-cyclic monophosphate content in isolated rat fat-cells

1974 ◽  
Vol 142 (2) ◽  
pp. 345-351 ◽  
Author(s):  
Kenneth Siddle ◽  
C. Nicholas Hales
Keyword(s):  
Cyclic Amp ◽  
Glucose Uptake ◽  
Local Anaesthetics ◽  
Inhibitory Effect ◽  
Fat Cells ◽  
Atp Content ◽  
Dibutyryl Cyclic Amp ◽  
Ion Movements ◽  
Rat Fat Cells ◽  
Isolated Rat

1. Local anaesthetics inhibited hormone-stimulated lipolysis in isolated rat fat-cells. The most potent anaesthetic was dibucaine, which inhibited adrenaline-stimulated lipolysis by 50% at a concentration of 0.16mm. 2. The amount of inhibition produced by a given concentration of anaesthetic was very similar with adrenaline, theophylline and dibutyryl cyclic AMP, at submaximal and maximal concentrations. 3. The inhibitory effect of dibucaine on lipolysis was apparent within 5 min and was constant over 1h. 4. Dibucaine inhibited basal, adrenaline-stimulated and insulin-stimulated glucose uptake at concentrations 6–10-fold higher than those inhibiting lipolysis. 5. The effects of dibucaine on lipolysis and glucose uptake were reversed after removal of anaesthetic and washing of cells. 6. Dibucaine further elevated the concentration of cyclic AMP in the presence of adrenaline or adrenaline plus theophylline. 7. Dibucaine had no effect on ATP content at concentrations causing 80% inhibition of lipolysis, but lowered ATP content at higher concentrations. 8. The relative potency of different local anaesthetics as inhibitors of hormone-stimulated lipolysis paralleled their potency as inhibitors of ion movements in other systems. 9. The possibility is discussed that Ca2+ions are involved in the regulation of lipolysis, and that local anaesthetics inhibit lipolysis by interfering with Ca2+translocation.

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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