Vasopressin stimulates cortisol secretion and phosphoinositide catabolism in cultured bovine adrenal fasciculata/reticularis cells

1990 ◽  
Vol 5 (2) ◽  
pp. 109-116 ◽  
Author(s):  
I. M. Bird ◽  
M. Nicol ◽  
B. C. Williams ◽  
S. W. Walker
Keyword(s):  
Maximal Response ◽  
Zona Fasciculata ◽  
Cortisol Secretion ◽  
Small Magnitude ◽  
Threshold Response ◽  
Similar Dose ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Cells Cultured

ABSTRACT Cells isolated from the zona fasciculata/reticularis (ZFR) of the bovine adrenal cortex and maintained in culture were found to secrete cortisol in response to vasopressin stimulation. The increased cortisol secretion was dose dependent, with a threshold response at 1 nm and a maximal response (1·68-fold over basal) at 0·1 μm. In cells cultured in the presence of [3H]inositol (to prelabel the membrane phosphoinositide pool), stimulation with vasopressin in the presence of LiCl (10 mm) resulted in a similar dose-dependent increase in labelling of the phosphoinositol fraction, with a maximal response (1·45-fold over basal) at 10 nm. The increased labelling of the phosphoinositol fraction was independent of extracellular Ca2+ as it was not abolished in medium with [Ca2+ ] buffered to intracellular resting levels. This suggests that vasopressin stimulation results in the activation of a phosphoinositidase C. It is probable that cortisol secretion by bovine ZFR cells in response to vasopressin is dependent upon activation of this Ca2+-independent phosphoinositidase C. However, the small magnitude of the cortisol secretory response makes it unlikely that vasopressin is a primary regulator of cortisol secretion in vivo.

Inhibition by nifedipine of endothelin-induced adrenal catecholamine secretion in anesthetized dogs

1993 ◽  
Vol 71 (3-4) ◽  
pp. 301-305 ◽  
Author(s):  
Nobuharu Yamaguchi
Keyword(s):  
Calcium Channels ◽  
Endothelin 1 ◽  
Aortic Blood ◽  
Similar Dose ◽  
Anesthetized Dogs ◽  
Underlying Mechanisms ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Initial Peak

The present study was conducted to investigate local effects of endothelin-1 (ET-1) on basal adrenal catecholamine (CA) secretion and underlying mechanisms of action of ET-1 in anesthetized dogs. ET-1 was locally administered to the left adrenal gland through a catheter inserted into the left adrenolumbar artery. Plasma CA concentrations in adrenal venous and aortic blood were determined by an HPLC–electrochemical method. The local infusions (1 min, 0.5 mL/min) of ET-1, in doses of 0.01, 0.1, and 1.0 μg/mL, resulted in a dose-dependent increase in epinephrine secretion, rising from an initial basal value of 6.9 ± 1.4 ng∙min−1∙g−1 to maximum values of 7.6 ± 1.5, 81.1 ± 38.3*, and 680.9 ± 107.6* ng∙min−1∙g−1 (*p < 0.05, n = 7), respectively. Neither mean arterial pressure nor plasma CA levels in aortic blood altered following ET-1 infusions. A similar dose-dependent increase in norepinephrine output was also observed with ET-1. Following the initial peak observed during infusion with the highest dose of ET-1, the output of both epinephrine and norepinephrine remained significantly elevated over a period of 30 min. This ET-1-induced, long-lasting increase in adrenal CA output was abolished by nifedipine (100 μg/mL) similarly administered 10 min before ET-1 infusion. The results indicate that ET-1 directly enhances the basal secretion of CA from dog adrenal medulla in vivo. The study suggests that the ET-1-induced increase in adrenal CA secretion is, at least in part, mediated by the opening of dihydropyridine-sensitive L-type calcium channels at the level of adrenal medullary chromaffin cells.Key words: adrenal catecholamines, anesthetized dogs, calcium channels, endothelin-1, epinephrine, intra-adrenolumbar arterial infusion, nifedipine, norepinephrine.

Leukotriene D4 induces MMP-1, which functions as an IGFBP protease in human airway smooth muscle cells

1996 ◽  
Vol 271 (6) ◽  
pp. L1014-L1022 ◽  
Author(s):  
R. Rajah ◽  
S. E. Nunn ◽  
D. J. Herrick ◽  
M. M. Grunstein ◽  
P. Cohen
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Airway Smooth Muscle Cells ◽  
Igf Binding Proteins ◽  
Leukotriene D4 ◽  
Igf Binding ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Insulin Like Growth Factors

We have previously demonstrated that the asthma-associated proinflammatory eicosanoid leukotriene D4 (LTD4) is comitogenic with insulin-like growth factors (IGF) in airway smooth muscle (ASM) cells. This synergistic effect of LTD4 and IGF on ASM cell growth involves proteolysis of ASM-produced inhibitory IGF-binding proteins (IGFBP). In this report, we analyzed the conditioned media (CM) from LTD4-treated human ASM cells (ASM-LTD4-CM) by Western ligand blotting and demonstrated a marked LTD4-induced reduction in the levels of the intact IGFBP (predominantly IGFBP-2) secreted by these cells. The IGFBP-2 in the ASM-LTD4-CM was identified as lower-molecular-weight fragments by Western immunoblotting. Incubation with 125I-labeled IGFBP demonstrated that an IGFBP protease was induced in the ASM cells in response to LTD4 treatment. Immunodepletion of ASM-LTD4-CM with anti-matrix metalloproteinase (MMP)-1 antibodies demonstrated a dose-dependent reduction of IGFBP proteolysis. Tissue inhibitor of MMP-1 and Batimastat (synthetic) inhibited proteolysis of IGFBP. Immunoblotting the ASM-LTD4-CM with anti-MMP-1 demonstrated a dose-dependent increase in MMP-1 protein. Similar results were also obtained by immunocytochemistry. Collectively, these observations demonstrate that MMP-1 is an IGFBP protease induced by leukotrienes that plays a significant role in modulating IGF action in ASM cells. A similar mechanism may be applicable in vivo in the airways of patients with asthma.

Parotid Gland Function in Streptozotocin-diabetic Rats

1987 ◽  
Vol 66 (2) ◽  
pp. 425-429 ◽  
Author(s):  
L.C. Anderson
Keyword(s):  
Protein Composition ◽  
Diabetic Rats ◽  
Response Threshold ◽  
Maximal Response ◽  
Parotid Glands ◽  
Threshold Response ◽  
Parotid Acinar Cells ◽  
Streptozotocin Diabetic Rats ◽  
Gland Function

The in vivo response of parotid glands to adrenergic, cholinergic, and peptidergic agonists was studied in control, streptozotocin- (one month's duration), and insulin-treated (three hr) diabetic rats. Neither diabetes nor insulin had an effect on the response to physalaemin. In contrast, physalaemin threshold-dose was lower and maximal response greater in control rats placed on a bulk diet. As previously described, diabetes resulted in nonparallel changes in parotid protein composition, including a reduction in amylase and an increase in peroxidase concentrations (mg/mg protein). In contrast to the results observed with physalaemin, response to methacholine was significantly reduced in diabetic animals, and could be restored to control levels by insulin. Placement of animals on a bulk-diet, however, had no effect on threshold response to methacholine. Finally, response threshold for epinephrine was unaffected by diabetes, insulin, or bulk diet. Thus, insulin appears, directly and specifically, to alter the response of parotid acinar cells to cholinergic stimulation.

EFFECTS OF GROWTH HORMONE, PROLACTIN AND THYROXINE ON BODY WEIGHT, SOMATOMEDIN-LIKE ACTIVITY AND IN-VIVO SULPHATION OF CARTILAGE IN HYPOPITUITARY DWARF MICE

1980 ◽  
Vol 85 (1) ◽  
pp. 35-47 ◽  
Author(s):  
A. T. HOLDER ◽  
M. WALLIS ◽  
P. BIGGS ◽  
M. A. PREECE
Keyword(s):  
Growth Hormone ◽  
Costal Cartilage ◽  
Tail Length ◽  
Bovine Growth Hormone ◽  
Dwarf Mouse ◽  
Dwarf Mice ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
In Vivo Uptake

SUMMARY Hypopituitary dwarf mice were found to have reduced levels of serum somatomedin-like activity compared with normal mice of the Snell strain. Treatment with bovine growth hormone for 3 and 7 days resulted in growth without significantly increased levels of serum somatomedin-like activity, as detected by in-vitro uptake of 35SO42− into normal rat cartilage; only after treatment for 14 days was somatomedin activity significantly raised. However, treatment for 2 days with bovine growth hormone, bovine prolactin or thyroxine resulted in a dose-dependent increase in in-vivo uptake of 35SO42− into dwarf mouse costal cartilage; growth hormone and thyroxine did not act synergistically. Ten days of treatment with growth hormone promoted a dose-dependent increase in both growth (increased weight gain and tail length) and in-vivo uptake of 35SO42−. Increase in tail length was correlated with uptake of 35SO42−. Thus, in-vivo uptake of 35SO42− into dwarf mouse costal cartilage provides a sensitive method for detecting a dose-related effect of growth hormone.

scholarly journals Folate protects against oxidative modification of human LDL

2001 ◽  
Vol 86 (6) ◽  
pp. 637-639 ◽  
Author(s):  
Emi Nakano ◽  
John A. Higgins ◽  
Hilary J. Powers
Keyword(s):  
Lag Time ◽  
Oxidative Modification ◽  
Protective Effects ◽  
Unsaturated Lipids ◽  
Anti Oxidant ◽  
Total Homocysteine ◽  
Endogenous Antioxidants ◽  
Dose Dependent Increase ◽  
Dose Dependent

Elevated plasma total homocysteine is considered to be a graded risk factor for cardiovascular disease. Folate, through its homocysteine-lowering potential, may therefore be protective. Folate, however, may have protective effects independent of homocysteine-lowering. We have measured the effects of folate on Cu-catalysed oxidative damage to the unsaturated lipids in human LDL. Experiments were carried out in the presence of citrate, and followed increases in absorption at 234 nm, which measures the amount of conjugated diene produced. There is a lag time during which endogenous antioxidants are oxidised, followed by rapid oxidation of lipid. Addition of 0–6 μM-5-methyltetrahydrofolate produced a dose-dependent increase in the lag time, suggesting that folate may have a direct anti-oxidant role in vivo, which is independent of any indirect effects through lowering of homocysteine levels.

scholarly journals Corticosteroid effect on murine hemopoietic precursor cells in vivo

Blood ◽  
1981 ◽  
Vol 57 (6) ◽  
pp. 1138-1139 ◽  
Author(s):  
E Niskanen ◽  
J Squires
Keyword(s):  
Colony Formation ◽  
Precursor Cells ◽  
Diffusion Chambers ◽  
Hemopoietic Precursor Cells ◽  
Granulocytic Colony ◽  
Dose Dependent Increase ◽  
Dose Dependent

Abstract The effect of methylprednisolone on murine hemopoietic colony formation in diffusion chambers implanted in mice was evaluated. A dose-dependent increase in granulocytic colony (CFU-DG) formation from murine marrow was observed. This effect could be abrogated by administration of progesterone. These studies suggest that the murine early granulocytic precursors (CFU-DG) have receptors that mediate proliferation-promoting signals triggered by glucocorticoids. Erythroid colony formation (CFU- DE) was not effected by methylprednisolone administration.

scholarly journals METABOLIC ACTIVATION OF 2,6-DIMETHYLANILINE: MUTATIONAL SPECIFICITY IN THE GPT GENE OF AS52 CELLS

2018 ◽  
Vol 11 (9) ◽  
pp. 394
Author(s):  
Seo Hyun Moon ◽  
Min Young Kim
Keyword(s):  
Parent Compound ◽  
Chinese Hamster ◽  
Relative Survival ◽  
Metabolic Activation ◽  
Nested Polymerase Chain Reaction ◽  
Trypan Blue Exclusion ◽  
Polymerase Chain ◽  
Dose Dependent Increase ◽  
Dose Dependent

Objective: The purpose of the current work was to characterize the mechanisms of cytotoxicity and mutagenesis of a potential human bladder carcinogen 2,6-dimethylaniline (2,6-DMA).Methods: Chinese hamster ovary (CHO) AS52 cells were exposed to either human S9 activated 2,6-DMA for 6 h or its N-hydroxylamine and aminophenol metabolites for 1 h in serum-free medium. Cell survival was determined by trypan blue exclusion 24 h after treatment, and 6-thioguanine-resistant mutants at the xanthine-guanine phosphoribosyl transferase (gpt) gene locus were assessed with doses, of which relative survival is 30% or more. Nested polymerase chain reaction-based deletion analysis was also performed.Results: AS52 cells exhibited a dose-dependent increase in cytotoxicity and mutant fraction on treatment of 2,6-DMA and its metabolites but show a considerable variation in potency with aminophenol metabolites having the highest potency and parent compound at least; at the highest 2,6-dimethylaminophenol dose (10 μM), the mutant fraction in AS52 cells was 8-fold (13.2×10−5) greater than the spontaneous fraction of 1.62×10−5. Total deletion of the gpt gene sequences was found in 1 (4%) spontaneous and 2 (6%) the 6-thioguanine mutants generated by N-hydroxy-2,6-DMA.Conclusions: These findings indicate the mutagenicity of 2,6-DMA at the gpt gene, which is mediated through hydroxylamine and aminophenol metabolites, and contribute to the elucidation of mechanisms through which 2,6-DMA may exert its effects in vivo.

Regional differences in constitutive and induced ICAM-1 expression in vivo

1995 ◽  
Vol 269 (6) ◽  
pp. H1955-H1964 ◽  
Author(s):  
J. Panes ◽  
M. A. Perry ◽  
D. C. Anderson ◽  
A. Manning ◽  
B. Leone ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Regional Differences ◽  
Time Course ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Fourfold Increase ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Higher Doses

The aim of the present study was to characterize and compare the expression of intercellular adhesion molecule 1 (ICAM-1) on unstimulated and endotoxin-challenged endothelial cells in different tissues of the rat. ICAM-1 expression was measured using 125I-labeled anti-rat ICAM-1 monoclonal antibody (MAb) and an isotype-matched control MAb labeled with 131I (to correct for nonspecific accumulation of the binding MAb). Under baseline conditions, ICAM-1 MAb binding was observed in all organs. The binding of 125I-ICAM-1 MAb varied widely among organs, with the largest accumulation (per g tissue) in the lung, followed by heart (1/30th of lung activity), splanchnic organs (1/50th of lung activity), thymus (1/100th of lung activity), testes (1/300th of lung activity), and skeletal muscle (1/800th of lung activity). Endotoxin induced an increase in ICAM-1 MAb binding in all organs except the spleen. Endotoxin-induced upregulation of ICAM-1 was greatest in heart and skeletal muscle (5- to 10-fold), whereas the remaining organs exhibited a two- to fourfold increase in ICAM-1 expression. Maximal upregulation of ICAM-1 occurred at 9-12 h after endotoxin administration. A dose-dependent increase in ICAM-1 expression was elicited by 0.1-10 microgram/kg, with higher doses (up to 5 mg/kg) producing no further increment. Induction of ICAM-1 mRNA after endotoxin was observed in all tissues examined (lung, heart, intestine), peaked at 3 h, and then rapidly returned to control levels. These findings indicate that ICAM-1 is constitutively expressed on vascular endothelium in all organs of the rat and that there are significant regional differences in the magnitude and time course of endotoxin-induced ICAM-1 expression.

scholarly journals Cardiac Effects of Echinocandins in Endotoxemic Rats

2015 ◽  
Vol 60 (1) ◽  
pp. 301-306 ◽  
Author(s):  
Christian Koch ◽  
Matthias Wolff ◽  
Michael Henrich ◽  
Markus A. Weigand ◽  
Christoph Lichtenstern ◽  
...  
Keyword(s):  
Cardiac Myocytes ◽  
Fungal Infections ◽  
Underlying Mechanism ◽  
Rank Test ◽  
Control Group ◽  
Endotoxemic Shock ◽  
And Control ◽  
Dose Dependent Increase ◽  
Dose Dependent

ABSTRACTEchinocandins are known as effective and safe agents for the prophylaxis and treatment of different cohorts of patients with fungal infections. Recent studies revealed that certain pharmacokinetics of echinocandin antifungals might impact clinical efficacy and safety in special patient populations. The aim of our study was to evaluate echinocandin-induced aggravation of cardiac impairment in septic shock. Using anin vivoendotoxemic shock model in rats, we assessed hemodynamic parameters and time to hemodynamic failure (THF) after additional central-venous application of anidulafungin (2.5 mg/kg of body weight [BW]), caspofungin (0.875 mg/kg BW), micafungin (3 mg/kg BW), and control (0.9% sodium chloride). In addition, echinocandin-induced cytotoxicity was evaluated in isolated rat cardiac myocytes. THF of the animals in the caspofungin group (n= 7) was significantly reduced compared to that in the control (n= 6) (136 min versus 180 min;P= 0.0209). The anidulafungin group (n= 7) also showed a trend of reduced THF (136 min versus 180 min; log-rank testP= 0.0578). Animals in the micafungin group (n= 7) did not show significant differences in THF compared to those in the control. Control group animals and also micafungin group animals did not show altered cardiac output (CO) during our experiments. In contrast, administration of anidulafungin or caspofungin induced a decrease in CO. We also revealed a dose-dependent increase of cytotoxicity in anidulafungin- and caspofungin-treated cardiac myocytes. Treatment with micafungin did not cause significantly increased cytotoxicity. Further studies are needed to explore the underlying mechanism.

Hydrocortisone treatment increases the sensitivity and responsiveness to cholecystokinin in rat pancreas

1989 ◽  
Vol 257 (3) ◽  
pp. G364-G370 ◽  
Author(s):  
M. Otsuki ◽  
Y. Okabayashi ◽  
T. Nakamura ◽  
M. Fujii ◽  
S. Tani ◽  
...  
Keyword(s):  
Ionophore A23187 ◽  
Pancreatic Acini ◽  
Cck Receptors ◽  
Cyclic Monophosphate ◽  
Dna Contents ◽  
Wet Weight ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Hydrocortisone Treatment

The effects of hydrocortisone treatment on the secretory abilities of pancreatic acini to various secretagogues were studied. Rats were given subcutaneous injections of hydrocortisone at doses of 1.25, 2.5, or 5.0 mg/kg body wt once daily for 7 days. Hydrocortisone led to a small dose-dependent increase in pancreatic wet weight per 100 g body wt, which was associated with an increase in both total protein and DNA contents. In acini prepared from hydrocortisone-treated rats, both the responsiveness and the sensitivity to cholecystokinin octapeptide (CCK-8) was increased. The concentration dependence of cellular Ca2+ mobilization in response to CCK-8 was also shifted to lower concentrations in acini from hydrocortisone-treated rats compared with control rat acini. In vivo administration of hydrocortisone caused a significant increase in the affinity of 125I-CCK-8 binding to high-affinity receptors. The secretory responsiveness to carbamylcholine and bombesin, but not to secretin, was also increased but without any change in the sensitivity. Moreover, the hydrocortisone treatment increased the secretory responsiveness of acini to the Ca2+ ionophore A23187 and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate but did not to an adenosine 3',5'-cyclic monophosphate analogue, 8-bromoadenosine 3',5'-cyclic monophosphate. The present observations suggest that in vivo glucocorticoid administration affects both the CCK receptors and a postreceptor loci.

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