Effects of omeprazole treatment on nucleoside transporter expression and adenosine uptake in rat gastric mucosa

2009 ◽  
Vol 87 (5) ◽  
pp. 402-410 ◽  
Author(s):  
Zoran B. Redzic ◽  
Fuad A. Hasan ◽  
Hameed Al-Sarraf
Keyword(s):  
Gastric Mucosa ◽  
Acid Secretion ◽  
Functional Activity ◽  
Transcript Level ◽  
Nucleoside Transporters ◽  
Mrna Levels ◽  
Nucleoside Transporter ◽  
Adenosine Uptake ◽  
Rat Gastric Mucosa

Increased adenosine concentration inhibits gastric acid secretion in rat via adenosine A1 and A2A receptors, whereas achlorhydria suppresses A1 and A2A receptor gene expression. This study aimed to examine the effects of omeprazole-induced achlorhydria on the expression and functional activity of nucleoside transporters in rat gastric mucosa. Wistar rats were treated for either 1 or 3 days with 0.4 mmol/kg omeprazole via gavage; controls were treated with vehicle. The expression of nucleoside transporters at the transcript level was explored by quantitative real-time polymerase chain reaction assays; the functional activity of nucleoside transporters in gastric mucosa was explored by observing [3H]adenosine uptake in vitro. Gastric mucosa expressed rat equilibrative nucleoside transporter (rENT) 1 and 2, and rat concentrative nucleoside transporter (rCNT) 1, 2, and 3 at the transcript level, and the estimated values for the threshold cycles for target amplification (Ct) were 31.5 ± 2, 28.5 ± 2.1, 32.9 ± 2.2, 29.1 ± 2, and 28.9 ± 2.5, respectively (n = 3 or 4). The Ct value for rat β-actin was 21.9 ± 1.8 (n = 4). In vitro uptake of [3H]adenosine by gastric mucosa samples consisted of Na+-dependent and Na+-independent components. One-day omeprazole treatment caused no change in nucleoside transporter mRNA levels or in [3H]adenosine uptake. Three-day omeprazole treatments, however, led to a 12-fold and 17-fold increase in rENT2 and rCNT1 mRNA levels, respectively. Samples taken after 3 days of treatment also took up significantly more [3H]adenosine than did samples from the corresponding control. In conclusion, the possible modification of nucleoside transport activities by changes in intraluminal acidity may have significance as part of a purinergic regulatory feedback mechanism in the control of gastric acid secretion.

scholarly journals 2-Nitroimidazole-Furanoside Derivatives for Hypoxia Imaging—Investigation of Nucleoside Transporter Interaction, 18F-Labeling and Preclinical PET Imaging

2019 ◽  
Vol 12 (1) ◽  
pp. 31
Author(s):  
Florian Maier ◽  
Anna Schweifer ◽  
Vijaya Damaraju ◽  
Carol Cass ◽  
Gregory Bowden ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Tumor Hypoxia ◽  
Radiochemical Yield ◽  
Nucleoside Transporters ◽  
Nucleoside Transporter ◽  
Hypoxia Imaging ◽  
Molar Activity ◽  
Slow Kinetics ◽  
Sugar Derivatives

The benefits of PET imaging of tumor hypoxia in patient management has been demonstrated in many examples and with various tracers over the last years. Although, the optimal hypoxia imaging agent has yet to be found, 2-nitroimidazole (azomycin) sugar derivatives—mimicking nucleosides—have proven their potential with [18F]FAZA ([18F]fluoro-azomycin-α-arabinoside) as a prominent representative in clinical use. Still, for all of these tracers, cellular uptake by passive diffusion is postulated with the disadvantage of slow kinetics and low tumor-to-background ratios. We recently evaluated [18F]fluoro-azomycin-β-deoxyriboside (β-[18F]FAZDR), with a structure more similar to nucleosides than [18F]FAZA and possible interaction with nucleoside transporters. For a deeper insight, we comparatively studied the interaction of FAZA, β-FAZA, α-FAZDR and β-FAZDR with nucleoside transporters (SLC29A1/2 and SLC28A1/2/3) in vitro, showing variable interactions of the compounds. The highest interactions being for β-FAZDR (IC50 124 ± 33 µM for SLC28A3), but also for FAZA with the non-nucleosidic α-configuration, the interactions were remarkable (290 ± 44 µM {SLC28A1}; 640 ± 10 µM {SLC28A2}). An improved synthesis was developed for β-FAZA. For a PET study in tumor-bearing mice, α-[18F]FAZDR was synthesized (radiochemical yield: 15.9 ± 9.0% (n = 3), max. 10.3 GBq, molar activity > 50 GBq/µmol) and compared to β-[18F]FAZDR and [18F]FMISO, the hypoxia imaging gold standard. We observed highest tumor-to-muscle ratios (TMR) for β-[18F]FAZDR already at 1 h p.i. (2.52 ± 0.94, n = 4) in comparison to [18F]FMISO (1.37 ± 0.11, n = 5) and α-[18F]FAZDR (1.93 ± 0.39, n = 4), with possible mediation by the involvement of nucleoside transporters. After 3 h p.i., TMR were not significantly different for all 3 tracers (2.5–3.0). Highest clearance from tumor tissue was observed for β-[18F]FAZDR (56.6 ± 6.8%, 2 h p.i.), followed by α-[18F]FAZDR (34.2 ± 7.5%) and [18F]FMISO (11.8 ± 6.5%). In conclusion, both isomers of [18F]FAZDR showed their potential as PET hypoxia tracers. Differences in uptake behavior may be attributed to a potential variable involvement of transport mechanisms.

Relationship between potassium, acid secretion and bioelectric potentials of frog gastric mucosa in the presence of histamine and thiocyanate

1959 ◽  
Vol 196 (6) ◽  
pp. 1266-1269 ◽  
Author(s):  
John B. Harris ◽  
Isidore S. Edelman
Keyword(s):  
Gastric Mucosa ◽  
Acid Secretion ◽  
Potassium Concentration ◽  
Hydrogen Ion ◽  
Ion Secretion ◽  
Transient Rise ◽  
Net Flux ◽  
Bioelectric Potentials ◽  
Sustained Increase

The transmucosal potential difference (PD), the rate of H+ secretion and the net flux of potassium from nutrient to secretory phases (JnsK) of the frog gastric mucosa were studied in vitro by the chamber method. Histamine produced a fall in PD, a sustained increase in H+ production and an equivocal rise in JnsK. Increasing the nutrient potassium concentration (Kn) to 8.5 mEq/l. in the presence of histamine induced a depression in PD, although the rate of acid secretion was unchanged. Hydrogen ion secretion decreased when the nutrient potassium concentration was decreased to 1 mEq/l. despite the continued presence of histamine. The response of JnsK to alterations in nutrient potassium concentration was unaffected by the presence of either histamine or thiocyanate. Thiocyanate produced almost complete inhibition of H+ secretion and a rise in PD. Raising the nutrient potassium concentration in the presence of thiocyanate produced a prompt and sustained fall in PD, followed by a transient rise when Kn was lowered. Alterations of the nutrient potassium concentration in the presence of thiocyanate had no effect on the rate of acidification. The data indicate that under certain circumstances PD and H+ secretion can be uncoupled and that the inverse relationship between Kn and PD is substantially independent of the rate of H+ secretion.

Role of fatty acid oxidation in mechanism of action of gastric secretagogues

1980 ◽  
Vol 238 (3) ◽  
pp. G255-G262
Author(s):  
J. Chacin ◽  
G. Martinez ◽  
E. Severin
Keyword(s):  
Fatty Acid ◽  
Gastric Mucosa ◽  
Acid Secretion ◽  
Fatty Acid Oxidation ◽  
Acid Oxidation ◽  
Primary Role ◽  
Dependent Manner ◽  
Beta Oxidation

The role of beta-oxidation in the mechanism of stimulation of acid secretion was examined in toad gastric mucosa in vitro. The incubation with 4-pentenoate selectively inhibited in a dose-dependent manner the rate of 14CO2 formation from [1-14C]octanoate. Pretreatment with 20 mM 4-pentenoate sharply reduced the respiratory and secretory responses to theophylline and histamine. Tracer studies showed a major utilization of exogenous octanoate over glucose and pyruvate by the in vitro toad gastric mucosa. Theophylline and histamine stimulated by 69% the rate of octanoate oxidation. Over 60% of the increments in oxygen uptake produced by theophylline and histamine accounted for the increments in octanoate oxidation, whereas glucose and pyruvate together accounted for less than 25%. Octanoate-dependent respiration was shown to correlate with octanoate oxidation under both inhibition with 4-pentenoate and stimulation with theophylline. Theophylline stimulated by 25% the rate of octanoate oxidation in Cl--free glucuronate-nutrient solutions. The present work provides further evidence for the primary role of fatty acid oxidation in the mechanism of acid secretion in amphibian.

Fludarabine uptake mechanisms in B-cell chronic lymphocytic leukemia

Blood ◽  
2003 ◽  
Vol 101 (6) ◽  
pp. 2328-2334 ◽  
Author(s):  
Mı́riam Molina-Arcas ◽  
Beatriz Bellosillo ◽  
F. Javier Casado ◽  
Emili Montserrat ◽  
Joan Gil ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Chronic Lymphocytic Leukemia ◽  
Expression Patterns ◽  
Individual Variability ◽  
Lymphocytic Leukemia ◽  
Mrna Levels ◽  
Nucleoside Transporter ◽  
Drug Bioavailability

Nucleoside derivatives are currently used in the treatment of hematologic malignancies. Although intracellular events involved in the pharmacologic action of these compounds have been extensively studied, the role of plasma membrane transporters in nucleoside-derived drug bioavailability and action in leukemia cells has not been comprehensively addressed. We have monitored the amounts of mRNA for the 5 nucleoside transporter isoforms cloned so far (CNT1, CNT2, CNT3, ENT1, and ENT2) in several human cell types and in normal human leukocytes. We then examined the expression patterns of these plasma membrane proteins in patients with chronic lymphocytic leukemia (CLL) and correlated them with in vitro fludarabine cytotoxicity. Despite a huge individual variability in the mRNA amounts for every transporter gene expressed in CLL cells (CNT2, CNT3, ENT1, and ENT2), no relationship between mRNA levels and in vitro fludarabine cytotoxicity was observed. Fludarabine accumulation in CLL cells was mostly, if not exclusively, mediated by ENT-type transporters whose biologic activity was clearly correlated with fludarabine cytotoxicity, which reveals a role of ENT-mediated uptake in drug responsiveness in patients with CLL.

scholarly journals Laminin mediates the restitution of rat gastric mucosa in vitro

1994 ◽  
Vol 79 (5) ◽  
pp. 647-659 ◽  
Author(s):  
MA Miller ◽  
NW Bunnett ◽  
HT Debas
Keyword(s):  
Gastric Mucosa ◽  
Rat Gastric Mucosa
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