CCK, bombesin, and carbachol stimulate c-fos, c-jun, and c-myc oncogene expression in rat pancreatic acini

1992 ◽  
Vol 263 (3) ◽  
pp. G327-G332 ◽  
Author(s):  
L. Lu ◽  
C. D. Logsdon
Keyword(s):  
Mrna Expression ◽  
Gastrointestinal Hormones ◽  
Mrna Levels ◽  
Pancreatic Acini ◽  
Myc Oncogene ◽  
Maximal Stimulation ◽  
High Affinity Site ◽  
Oncogene Activation ◽  
Stimulation Of

To identify possible nuclear signals mediating long-term regulation of the pancreas by gastrointestinal hormones, the expression of c-fos, c-jun, and c-myc was investigated in rat pancreatic acini. Stimulation of the acini with cholecystokinin octapeptide (CCK-8, 100 pM), bombesin (10 nM), or carbachol (10 microM), but not gastrin (100 nM), secretin (100 nM), or vasoactive intestinal peptide (10 nM) induced an increase in oncogene mRNA expression. The percent increases of c-fos, c-jun, and c-myc mRNA were 207 +/- 40, 171 +/- 26, and 46 +/- 19 (n = 5) for CCK-8; 223 +/- 71, 159 +/- 31, and 43 +/- 21 (n = 5) for bombesin; and 125 +/- 51, 123 +/- 58, and 67 +/- 19 (n = 5) for carbachol, respectively. CCK-induced increases in oncogene mRNA were rapid and transient. c-fos and c-jun mRNA levels were increased after 30 min stimulation, peaked at 1 h, and returned to basal level in 2 h. Activation of c-myc was more prolonged with levels remaining elevated for at least 3 h. The effects of CCK-8 were concentration dependent. Detectable stimulation was seen at 10 pM; maximal stimulation occurred at 10 nM and was not affected by further increase in the concentration of CCK-8. JMV-180, a high-affinity site CCK receptor agonist and low-affinity site antagonist, alone did not stimulate c-fos mRNA expression but inhibited c-fos mRNA expression induced by CCK-8. These results suggest that the interaction between CCK and the low-affinity state of the CCK receptor is responsible for oncogene activation.

scholarly journals Sex Differences in Estrogen-Dependent Transcription of Gonadotropin-Releasing Hormone (GnRH) Gene Revealed in GnRH Transgenic Mice

Endocrinology ◽  
2003 ◽  
Vol 144 (8) ◽  
pp. 3351-3358 ◽  
Author(s):  
Niren R. Thanky ◽  
Ruth Slater ◽  
Allan E. Herbison
Keyword(s):  
Transgenic Mice ◽  
Mrna Expression ◽  
Gene Transcription ◽  
Transgene Expression ◽  
Gonadal Steroids ◽  
Critical Element ◽  
Sexually Dimorphic ◽  
Mrna Levels ◽  
Estrogen Replacement

Abstract The mechanisms through which gonadal steroids exert feedback actions on the activity of the GnRH neurons are not understood. Using a series of GnRH-LacZ transgenic mice we have examined the manner in which gonadal steroids suppress GnRH mRNA expression in male and female mice. The long-term gonadectomy of 5.5-GNZ-3.5 transgenic mice resulted in significant increases in cellular GnRH mRNA expression (P < 0.05) and plasma LH concentrations (P < 0.01) in both sexes. However, cellular levels of LacZ mRNA and β-galactosidase, which provide an index of GnRH gene transcription, were only elevated in males after gonadectomy. This sexually differentiated response was also observed in mice gonadectomized for 2 wk. Estrogen replacement in gonadectomized males returned transgene expression to intact levels. Experiments in transgenic mice with 3′ and 5′ deleted GnRH-LacZ constructs revealed that the suppressive influence of estrogen on LacZ transcription in the male required a critical element located between −5.2 and −1.7 kb of the GnRH promoter. These studies show that the suppression of GnRH mRNA expression by estrogen in the male involves a decrease in GnRH gene transcription that is dependent on a distal GnRH promoter element. The same mechanism does not exist in females, indicating that gonadal steroids suppress GnRH mRNA levels in a sexually dimorphic manner.

Elevated Expression of the NLRP3 Inflammasome and Its Correlation with Disease Activity in Adult-onset Still Disease

2017 ◽  
Vol 44 (8) ◽  
pp. 1142-1150 ◽  
Author(s):  
Chia-Wei Hsieh ◽  
Yi-Ming Chen ◽  
Chi-Chen Lin ◽  
Kuo-Tung Tang ◽  
Hsin-Hua Chen ◽  
...  
Keyword(s):  
Disease Activity ◽  
Mrna Expression ◽  
Nlrp3 Inflammasome ◽  
Mononuclear Cells ◽  
Mrna Levels ◽  
Adult Onset ◽  
Peripheral Blood Mononuclear ◽  
Protein Expressions ◽  
Still Disease ◽  
Stimulation Of

Objective.The dysregulation of the NLRP3 (NLR containing a pyrin domain) inflammasome is involved in autoinflammatory diseases. Adult-onset Still disease (AOSD) is regarded as an autoinflammatory disease. However, the pathogenic involvement of NLRP3 inflammasome in AOSD remains unclear and NLRP3 activators in AOSD are currently unknown.Methods.The mRNA expression of NLRP3 inflammasome signaling in peripheral blood mononuclear cells (PBMC) from 34 patients with AOSD and 14 healthy subjects was determined using quantitative-PCR (qPCR). The changes in mRNA and protein levels of NLRP3 inflammasome signaling in PBMC treated with the potential activator [imiquimod (IMQ)] or inhibitor of NLRP3 were evaluated using qPCR and immunoblotting, respectively. The supernatant levels of interleukin (IL)-1β and IL-18 were determined by ELISA.Results.Significantly higher mRNA levels of NLRP3 inflammasome signaling were observed in patients with AOSD compared with healthy controls. NLRP3 expressions were positively correlated with disease activity in patients with AOSD. IMQ (an effective Toll-like receptor 7 ligand; 10 µg/ml and 25 µg/ml) stimulation of PBMC from patients with AOSD induced dose-dependent increases of mRNA expression of NLRP3 (mean ± standard error of the mean, 2.06 ± 0.46 and 6.05 ± 1.84, respectively), caspase-1 (1.81 ± 0.23 and 4.25 ± 0.48), IL-1β (5.68 ± 1.51 and 12.13 ± 3.71), and IL-18 (2.32 ± 0.37 and 4.81 ± 0.51) compared with controls (all p < 0.005). IMQ stimulation of PBMC from patients similarly induced greater increases in protein expressions of NLRP3 inflammasome compared with controls. The protein expressions of NLRP3, IL-1β, and IL-18 on PBMC significantly decreased after treatment with NLRP3 inhibitor in patients with AOSD.Conclusion.Increased expression of NLRP3 inflammasome and its positive correlation with disease activity in AOSD suggest its involvement in disease pathogenesis. IMQ upregulated expressions of NLRP3 inflammasome signaling, and IMQ might be an activator of NLRP3 inflammasome in AOSD.

Regulation of intestinal cholecystokinin and somatostatin mRNA by bombesin in rats

1991 ◽  
Vol 261 (1) ◽  
pp. G71-G77 ◽  
Author(s):  
S. Kanayama ◽  
R. A. Liddle
Keyword(s):  
Steady State ◽  
Effective Dose ◽  
Trypsin Inhibitor ◽  
Gastrointestinal Hormones ◽  
Soybean Trypsin Inhibitor ◽  
Mrna Levels ◽  
Intravenous Infusions ◽  
Basal Plasma ◽  
Stimulation Of ◽  
Cck Release

The neuropeptide bombesin has been shown to stimulate secretion of several gastrointestinal hormones, including cholecystokinin (CCK). We have previously demonstrated that stimulation of CCK release by feeding is associated with an increase in steady-state intestinal CCK mRNA levels. The purpose of the present study was to determine whether bombesin stimulates CCK release in rats and, if so, to determine whether bombesin regulates CCK mRNA levels in a manner similar to that of feeding. To establish a proper dose of bombesin for stimulating CCK release, rats received 1-h intravenous infusions of 0.25, 1, 4, or 16 micrograms.kg-1.h-1 bombesin. Basal plasma CCK levels averaged 1.8 +/- 0.4 pM and increased to peak levels of 2.9 +/- 0.6 pM within 15 min of infusion with 4 micrograms.kg-1.h-1 bombesin (the maximally effective dose). With the use of this dose, rats then received infusions of bombesin or saline lasting up to 24 h. At 1, 2, 4, and 24 h, animals were killed for collection of plasma for CCK measurements and of intestine for measurements of intestinal CCK and somatostatin mRNA levels. Bombesin treatment stimulated an increase in plasma CCK levels at 1 h, but levels declined to basal by 4 h, where they remained at 24 h. Despite increasing plasma CCK levels, bombesin infusion, unlike dietary stimulation, had no effect on duodenal CCK mRNA levels. Finally, to determine whether the decrease in plasma CCK levels after prolonged bombesin treatment was due to tachyphylaxis, rats treated with bombesin for 4 h were also fed soybean trypsin inhibitor (a known stimulus of CCK secretion).(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin action in pancreatic acini from streptozotocin-treated rats. II. Binding of 125I-insulin to receptors

1981 ◽  
Vol 240 (1) ◽  
pp. G63-G68 ◽  
Author(s):  
H. Sankaran ◽  
Y. Iwamoto ◽  
M. Korc ◽  
J. A. Williams ◽  
I. D. Goldfine
Keyword(s):  
Protein Synthesis ◽  
Binding Sites ◽  
Insulin Binding ◽  
Diabetic Rats ◽  
Cell Protein ◽  
Scatchard Analysis ◽  
Pancreatic Acini ◽  
Maximal Stimulation ◽  
Major Class ◽  
Stimulation Of

The binding of 125I-insulin to its receptors was investigated with isolated pancreatic acini obtained from diabetic rats under incubation conditions identical to those used to study the effects of insulin on acinar cell protein synthesis. Binding was specific, time dependent, reversible, and linearly related to the acinar protein content. Degradation of insulin after 30 min of incubation was less than 10% of the total hormone present in the incubation medium. 125I-insulin dissociated from acini with a one-half time of 9 min. Unlabeled insulin at 83.5 nM accelerated the rate of dissociation of labeled insulin. 125I-insulin binding to acini was competitively inhibited by insulin and its analogues in proportion to their biological potencies. Scatchard analysis revealed a major class of insulin-binding sites with a Kd of 1.6 nM; maximal stimulation of protein synthesis was observed when > 90% of these high-affinity receptors were occupied. These studies indicate, therefore, that insulin binding to receptors on pancreatic acini can be correlated with subsequent regulation of biological functions.

Heregulin-α and heregulin-β expression is linked to a COX-2-PGE2 pathway in human gastric fibroblasts

2006 ◽  
Vol 290 (6) ◽  
pp. G1243-G1251 ◽  
Author(s):  
Kazuhiro Nagata ◽  
Ken Wada ◽  
Atsushi Tatsuguchi ◽  
Seiji Futagami ◽  
Katya Gudis ◽  
...  
Keyword(s):  
Gastric Ulcer ◽  
Growth Factor ◽  
Mrna Expression ◽  
Repair Process ◽  
Inhibitory Effect ◽  
Mrna Levels ◽  
Real Time Quantitative Pcr ◽  
Growth Factor Production ◽  
Cox 2 ◽  
Stimulation Of

We have previously shown heregulin (HRG)-α expression in human gastric fibroblasts and its stimulation of gastric epithelial cell growth. Although cyclooxygenase (COX)-2 has also been shown to stimulate growth factor production in these cells, the interaction between COX-2 and HRG remains unknown. Conditioned media (CM) from gastric fibroblasts incubated with PGE2 or interleukin (IL)-1β, a well known COX-2 inducer, were analyzed for their effect on erbB3 tyrosine phosphorylation in MKN28 gastric epithelial cells. HRG protein expression in fibroblast lysates and CM was also examined by western blot. HRG-α and HRG-β mRNA expression in gastric fibroblasts and human gastric tissue was examined by real-time quantitative PCR. HRG and COX-2 expressions in surgical resections of human gastric ulcer tissue were examined immunohistochemically. CM from fibroblasts incubated with PGE2, or IL-1β, stimulated erbB3 phosphorylation in MKN28 cells. Preincubation of the fibroblasts with celecoxib, a selective COX-2 inhibitor, suppressed CM-induced erbB3 phosphorylation. This inhibition was reversed by exogenous PGE2. As with erbB3 phophorylation, IL-1β stimulated both HRG-α and HRG-β mRNA expression, as well as HRG release into gastric fibroblast CM. IL-1β-stimulated HRG expression and release were also inhibited by celecoxib, and exogenous PGE2 restored this inhibitory effect, suggesting the activation of an IL-1β-COX-2-PGE2 pathway that culminates in the release of HRG from fibroblasts. HRG-α and HRG-β mRNA levels were significantly higher in gastric ulcer tissue than in normal gastric mucosa. HRG immunoreactivity was found in interstitial cells of the gastric ulcer bed and coexpressed with COX-2. These results suggest that HRG might be a new member of the growth factor family involved in the COX-2-dependent ulcer repair process.

scholarly journals Exploring the mRNA expression level of RELN in peripheral blood of schizophrenia patients before and after antipsychotic treatment

2020 ◽  
Author(s):  
Jiajun Yin ◽  
Yana Lu ◽  
Shui Yu ◽  
Zhanzhan Dai ◽  
Fuquan Zhang ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Peripheral Blood ◽  
Antipsychotic Treatment ◽  
Mrna Levels ◽  
Healthy Controls ◽  
Quantitative Real Time Pcr ◽  
Expression Levels ◽  
Before And After ◽  
The Brain

Abstract Background: The Reelin (RELN) gene encodes the protein reelin, which is a large extracellular matrix glycoprotein that plays a key role in brain development. Additionally, this protein may be involved in memory formation, neurotransmission, and synaptic plasticity, which have been shown to be disrupted in schizophrenia (SCZ). A decreasing trend in the expression of RELN mRNA in the brain and peripheral blood of SCZ patients has been observed. There is a need to determine whether changes in RELN mRNA expression in SCZ patients are the result of long-term antipsychotic treatment rather than the etiological characteristics of schizophrenia. The expression levels of RELN mRNA in the peripheral blood of 48 healthy controls and 30 SCZ patients before and after 12-weeks of treatment were measured using quantitative real-time PCR.Results: The expression levels of RELN mRNA in the SCZ group were significantly lower than that of healthy controls; however, after 12-weeks of antipsychotic treatment, RELN mRNA levels were significantly increased in the SCZ group.Conclusion: The up-regulation of RELN mRNA expression was current in SCZ patients after antipsychotic treatment, suggesting that the changes in RELN mRNA expression were related to the effect of the antipsychotic treatment.

Bombesin-induced residual stimulation of amylase release from mouse pancreatic acini

1985 ◽  
Vol 248 (2) ◽  
pp. G196-G199
Author(s):  
J. M. Howard ◽  
R. T. Jensen ◽  
J. D. Gardner
Keyword(s):  
Incubation Medium ◽  
Amylase Release ◽  
Pancreatic Acini ◽  
Mouse Pancreas ◽  
Gastrin Releasing Peptide ◽  
Maximal Stimulation ◽  
Incubation Solution ◽  
Significant Stimulation ◽  
Per Se ◽  
Stimulation Of

When dispersed acini from mouse pancreas are first incubated with bombesin, washed, and then reincubated with fresh incubation solution containing no bombesin, there is significant residual stimulation of amylase release. Induction of residual stimulation is relatively rapid in that significant stimulation occurs as early as after 15's of first incubation with bombesin. Induction of residual stimulation of amylase release per se is temperature independent, but induction does occur more rapidly when acini are first incubated at 37 degrees C than when they are first incubated at 4 degrees C. Residual stimulation of amylase release persists for at least 75 min in acini that have been first incubated with bombesin at 37 degrees C. The maximal residual stimulation of amylase release obtained with pancreatic acini that have been first incubated with bombesin and then washed is 45% greater than the maximal stimulation obtained when bombesin is added directly to the incubation medium. In terms of their abilities to cause residual stimulation of amylase release, litorin and ranatensin are equal to bombesin in potency and efficacy. Gastrin-releasing peptide is approximately 70% as efficacious as bombesin in causing residual stimulation of amylase release.

ASSESSMENT OF A TEST OF ADRENOCORTICAL FUNCTION USING β1–25 CORTICOTROPHIN

1969 ◽  
Vol 44 (4) ◽  
pp. 513-516
Author(s):  
K. WHALEY ◽  
W. P. SOUTTER ◽  
W. C. DICK ◽  
G. NUKI ◽  
W. W. DOWNIE
Keyword(s):  
Adrenal Cortex ◽  
Corticosteroid Therapy ◽  
Adrenocortical Function ◽  
Normal Range ◽  
Simple Method ◽  
Maximal Stimulation ◽  
Synthetic Polypeptides ◽  
Range Of Values ◽  
Stimulation Of

SUMMARY In ten patients with a variety of rheumatic disorders the changes in plasma corticosteroid (11-OHCS) levels have been studied after adrenocortical stimulation by a continuous 5 hr. infusion of Synacthen (Ciba) or by a single i.v. injection of 200 i.u. (320 μg.) Pentacosactride (Sandoz). Comparable increases were obtained using both synthetic polypeptides. It is suggested that administration of Pentacosactride intravenously is a simple method of obtaining prolonged maximal stimulation of the adrenal cortex. A normal range of values of plasma 11-OHCS, obtained from 28 subjects, is given, and it is shown that the results are reproducible. The results of tests in six subjects with secondary adrenal atrophy due to long-term corticosteroid therapy indicate that the test can discriminate between normal and subnormal adrenocortical function.

G protein in stimulation of PI hydrolysis by CCK in isolated rat pancreatic acinar cells

1988 ◽  
Vol 255 (5) ◽  
pp. E652-E659 ◽  
Author(s):  
T. Matozaki ◽  
C. Sakamoto ◽  
M. Nagao ◽  
H. Nishizaki ◽  
S. Baba
Keyword(s):  
G Protein ◽  
Inositol Phosphates ◽  
Inositol Phosphate ◽  
Secretory Rate ◽  
Amylase Release ◽  
Pancreatic Acini ◽  
Phosphate Accumulation ◽  
Maximal Stimulation ◽  
Inositol Phosphate Accumulation ◽  
Stimulation Of

To clarify the possible role of a guanine nucleotide-binding protein (G protein) in the signal transducing system activated by cholecystokinin (CCK), actions of CCK on rat pancreatic acini were compared with those of fluoride, a well-known activator of stimulatory (Gs) or inhibitory (Gi) G protein. When acini were incubated with increasing concentrations of either CCK-octapeptide (CCK8) or NaF, a maximal stimulation of amylase release from acini occurred at 100 pM CCK8 or 10 mM NaF, respectively; this secretory rate decreased as CCK8 or NaF concentration was increased. NaF caused an increased in cytoplasmic Ca2+ concentration from the internal Ca2+ store and stimulated accumulation of inositol phosphates in acini, as observed with CCK. However, NaF-stimulated Ca2+ mobilization had a lag period before detectable stimulation and was potentiated by AlCl3. These stimulatory effects of NaF appeared to be independent of cellular adenosine 3',5'-cyclic monophosphate (cAMP). Pretreatment with cholera toxin or pertussis toxin did not affect CCK8- or NaF-induced inositol phosphate accumulation or Ca2+ mobilization. 5'-Guanylimidodiphosphate activated the generation of inositol phosphates in the [3H]inositol-labeled pancreatic acinar cell membrane preparation, with half-maximal and maximal stimulation at 1 and 10 microM, respectively. Furthermore, the effects of submaximal CCK concentrations on inositol phosphate accumulation in membranes were markedly potentiated in the presence of 100 microM GTP, which alone was ineffective. Combined findings of the present study strongly suggest that pancreatic CCK receptors are probably coupled to the activation of polyphosphoinositide (PI) breakdown by a G protein, which appears to be fluoride sensitive but is other than Gs- or Gi-like protein.

Effect of extracellular manganese on amylase release from dispersed pancreatic acini

1981 ◽  
Vol 241 (5) ◽  
pp. G359-G364 ◽  
Author(s):  
S. Abdelmoumene ◽  
J. D. Gardner
Keyword(s):  
Secretory Process ◽  
Amylase Secretion ◽  
Enzyme Release ◽  
Amylase Release ◽  
Pancreatic Acini ◽  
Fourfold Increase ◽  
Maximal Stimulation ◽  
Basal Release ◽  
Induced Changes ◽  
Stimulation Of

In dispersed acini from guinea pig pancreas, adding extracellular manganese increased amylase release. A significant effect could be detected with 0.25 mM manganese, and maximal stimulation occurred with 1 mM manganese. When manganese was added, the rate of amylase release did not change during the first 20 min of incubation and then gradually increased to a new steady state by 80 min, which with 1 mM manganese represented a fourfold increase in the rate of enzyme release. Extracellular manganese inhibited the stimulation of amylase release caused by those secretagogues that mobilize cellular calcium but augmented the stimulation caused by those secretagogues whose actions are mediated by cellular cAMP. The mechanism by which manganese altered stimulated amylase secretion differed from the mechanism by which manganese stimulated basal amylase release because the change in stimulated release was maximal within 10 min, whereas the change in basal release did not occur until after 20 min. The actions of manganese on secretagogue-stimulated amylase release were not attributable to manganese-induced changes in secretagogue-stimulated calcium outflux or cAMP and, instead, appear to result from actions of manganese on one of the later steps in the mechanisms for stimulating the secretory process.

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