Inhibition of gastric H+ secretion, K+-ATPase and K+-phosphatase by estradiol in vivo and in vitro

1982 ◽  
Vol 60 (5) ◽  
pp. 680-684 ◽  
Author(s):  
L. Limlomwongse ◽  
P. Piyachaturawat
Keyword(s):  
Gastric Mucosa ◽  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Enzyme Activities ◽  
Direct Action ◽  
Inhibitory Effect ◽  
Secretory Rate ◽  
Dose Dependent

The effect of estrogen on the gastric acid secretion and H+-transporting enzymes, K+ -ATPase and K+-phosphatase, were investigated in the rat. The maximum H+ secretory rate in response to 1 mM histamine was significantly reduced (P < 0.05) in both the isolated gastric mucosa obtained from the rats treated with estradiol in vivo for 7 days and the mucosa directly incubated in vitro with estradiol. The inhibitory effect on the gastric enzyme activities in vitro showed a dose-dependent pattern of a noncompetitive type. The result suggested that estradiol may have a direct action on the gastric H+ secretion by inhibiting the H+ transport enzyme activities.

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.

scholarly journals In vitro inhibitory effect of obtusofolin on the activity of CYP3A4, 2C9, and 2E1

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Na Liu ◽  
Ping Chen ◽  
Xiaojun Du ◽  
Junxia Sun ◽  
Shasha Han
Keyword(s):  
Human Liver ◽  
Competitive Inhibition ◽  
Liver Microsomes ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Cytochrome P450 Enzymes ◽  
Inhibition Model ◽  
Dose Dependent

Abstract Background Obtusofolin is the major active ingredient of Catsia tora L., which possesses the activity of improving eyesight and protecting the optic nerve. Investigation on the interaction of obtusofolin with cytochrome P450 enzymes (CYP450s) could provide a reference for the clinical application of obtusofolin. Methods The effect of obtusofolin on the activity of CYP450s was investigated in the presence of 100 μM obtusofolin in pooled human liver microsomes (HLMs) and fitted with the Lineweaver–Burk plots to characterize the specific inhibition model and kinetic parameters. Results Obtusofolin was found to significantly inhibited the activity of CYP3A4, 2C9, and 2E1. In the presence of 0, 2.5, 5, 10, 25, 50, and 100 μM obtusofolin, the inhibition of these CYP450s showed a dose-dependent manner with the IC50 values of 17.1 ± 0.25, 10.8 ± 0.13, and 15.5 ± 0.16 μM, respectively. The inhibition of CYP3A4 was best fitted with the non-competitive inhibition model with the Ki value of 8.82 μM. While the inhibition of CYP2C9 and 2E1 was competitive with the Ki values of 5.54 and 7.79 μM, respectively. After incubating for 0, 5, 10, 15, and 30 min, the inhibition of CYP3A4 was revealed to be time-dependent with the KI value of 4.87 μM− 1 and the Kinact value of 0.0515 min− 1. Conclusions The in vitro inhibitory effect of obtusofolin implying the potential drug-drug interaction between obtusofolin and corresponding substrates, which needs further in vivo validations.

Antinociceptive properties of shikonin: in vitro and in vivo studies

2016 ◽  
Vol 94 (7) ◽  
pp. 788-796 ◽  
Author(s):  
Bhawana Gupta ◽  
Sabyasachi Chakraborty ◽  
Soumya Saha ◽  
Sunita Gulabsingh Chandel ◽  
Atul Kumar Baranwal ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Inhibitory Effect ◽  
Pain Modulation ◽  
In Vivo Studies ◽  
Channel Modulation ◽  
Pain Models ◽  
A Cell ◽  
Dose Dependent

Shikonin possess a diverse spectrum of pharmacological properties in multiple therapeutic areas. However, the nociceptive effect of shikonin is not largely known. To investigate the antinociceptive potential of shikonin, panel of GPCRs, ion channels, and enzymes involved in pain pathogenesis were studied. To evaluate the translation of shikonin efficacy in vivo, it was tested in 3 established rat pain models. Our study reveals that shikonin has significant inhibitory effect on pan sodium channel/N1E115 and NaV1.7 channel with half maximal inhibitory concentration (IC50) value of 7.6 μmol/L and 6.4 μmol/L, respectively, in a cell-based assay. Shikonin exerted significant dose dependent antinociceptive activity at doses of 0.08%, 0.05%, and 0.02% w/v in pinch pain model. In mechanical hyperalgesia model, dose of 10 and 3 mg/kg (intraperitoneal) produced dose-dependent analgesia and showed 67% and 35% reversal of hyperalgesia respectively at 0.5 h. Following oral administration, it showed 39% reversal at 30 mg/kg dose. When tested in first phase of formalin induced pain, shikonin at 10 mg/kg dose inhibited paw flinching by ∼71%. In all studied preclinical models, analgesic effect was similar or better than standard analgesic drugs. The present study unveils the mechanistic role of shikonin on pain modulation, predominantly via sodium channel modulation, suggesting that shikonin could be developed as a potential pain blocker.

Radioreceptor and biological characterization of cholecystokinin and gastrin in the chicken

1984 ◽  
Vol 246 (3) ◽  
pp. G296-G304
Author(s):  
S. R. Vigna
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Amylase Secretion ◽  
Physiological Regulation ◽  
Chicken Brain ◽  
Specific Radioimmunoassay ◽  
Cck Receptor Antagonist

Radioimmunoassay, radioreceptor assays, and bioassays were used to demonstrate that chicken brain and antrum extracts contain cholecystokinin (CCK)-like and gastrinlike peptides, respectively. C-terminal-specific radioimmunoassay of partially purified chicken CCK and gastrin gave dilution curves parallel to those of the mammalian peptides. Mouse cerebral cortical and rat pancreatic membrane radioreceptor assays were used to differentiate CCK- from gastrinlike peptides on the basis of the different CCK versus gastrin specificities of the two receptors. Confirmation of the biological activity of chicken brain CCK was obtained by stimulation of amylase secretion from rat pancreatic lobules in vitro. The specificity of this response was demonstrated by the inhibition of chicken CCK-stimulated amylase secretion by the specific CCK receptor antagonist dibutyryl cGMP. Chicken antral gastrin stimulated gastric acid secretion from the rat stomach in vivo. In contrast to previous hypotheses, it is proposed that chickens have significant amounts of an antral gastrinlike peptide and that therefore it is possible that gastrin is involved in the physiological regulation of gastric acid secretion in chickens.

scholarly journals Effects of Systemic Fluoride and in vitro Fluoride Treatment on Enamel Crystals

2006 ◽  
Vol 85 (11) ◽  
pp. 1042-1045 ◽  
Author(s):  
H. Chen ◽  
A. Czajka-Jakubowska ◽  
N.J. Spencer ◽  
J.F. Mansfield ◽  
C. Robinson ◽  
...  
Keyword(s):  
Surface Roughness ◽  
Crystal Surface ◽  
Direct Action ◽  
Crystal Surfaces ◽  
Surface Restructuring ◽  
Fluoride Treatment ◽  
Enamel Crystal ◽  
Dose Dependent

Systemically administered fluoride at a concentration of 75 ppm increases the surface roughness of developing enamel crystals in rats, which may be significant in advancing our understanding of the biological mechanism of fluorosis. Thus, the aim of this study was to investigate whether the increased surface roughness may be a result of surface restructuring by the direct action of fluoride at the crystal surface. We examined the fluoride dose-dependent roughening of enamel crystal surfaces in vivo, in the rat, and whether this roughening could be mimicked by the in vitro treatment of rat enamel crystals with neutral pH fluoride solutions. Our results showed that enamel crystal surface roughness increased after treatment with increasing fluoride ion concentrations, whether applied in vitro or administered systemically. This suggests a mechanism, alongside others, for the increased surface roughness of crystals in fluorotic enamel.

Oxygenation of frog gastric mucosa in vitro

1975 ◽  
Vol 229 (6) ◽  
pp. 1510-1513 ◽  
Author(s):  
GW Kidder ◽  
CW Montgomery
Keyword(s):  
Oxygen Consumption ◽  
Gastric Mucosa ◽  
Acid Secretion ◽  
Normal Pressure ◽  
Bathing Solution ◽  
Hyperbaric Chamber ◽  
Secretory Rate ◽  
Co2 Diffusion ◽  
Rate Of Oxygen Consumption

We have recently shown that 5% CO2/95% O2 in the serosal bathing solution, with 100% O2 in the mucosal solution, results in CO2-diffusion limitation of acid secretion in bullfrog gastric mucosa. Changing to 10% CO2/90% 02 on both surfaces doubles the acid secretory rate. We calculate that, were the rate of oxygen consumption to increase significantly as a result of secretory stimulation, the tissue would now be oxygen limited. This prediction is tested by raising the P02 by increasing the total pressure in a hyperbaric chamber. Since no change in acid secretory rate or potential difference was observed upon changing from PO2 = 0.9 to PO2 = 1.9 atm, we conclude that the tissue is not O2 limited at normal pressure. Decreasing PO2 below 0.9 atm, by contrast, decreases the acid secretory rate and raises both PD and resistance. We infer that the rate of oxygen consumption did not rise significantly when acid secretion was increased by supplying sufficient CO2.

Effect of catecholamines on somatostatin secretion by isolated perfused rat stomach

1981 ◽  
Vol 240 (3) ◽  
pp. E274-E278
Author(s):  
Y. Goto ◽  
M. Berelowitz ◽  
L. A. Frohman
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Rat Stomach ◽  
Beta Adrenergic ◽  
Somatostatin Secretion ◽  
Adrenergic Mechanism ◽  
Dose Dependent

The secretion of somatostatin-like immunoreactivity (SRIF-LI) by the isolated perfused rat stomach was studied in response to stimulation by catecholamines. Gastric SRIF-LI secretion was significantly stimulated in a dose-dependent manner by norepinephrine at 10(-6) and 10(-8) M, and the effect of norepinephrine (10(-8) M) was attenuated by the addition of propranolol (10(-6) M) but not of phentolamine (10(-6) M). SRIF-LI secretion was also stimulated by dopamine at concentrations of 10(-4) and 10(-6) M but not at 10(-8) M. The effect of dopamine (10(-6) M) was not altered by the addition of haloperidol (10(-4) to 10(-7)) or metoclopramide (10(-4) M), and bromocriptine (10(-6) M) was without effect on SRIF-LI secretion. These results suggest that gastric SRIF-LI secretion is stimulated by a beta-adrenergic mechanism and raise the possibility that gastric somatostatin contributes to the inhibitory effect of norepinephrine on gastric acid secretion.

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