Effects of omeprazole treatment on nucleoside transporter expression and adenosine uptake in 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 beta-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.
Redzic
Zoran B
ZB
Department of Physiology, Faculty of Medicine, Kuwait University, P.O. Box 24923, Safat 13110 Kuwait. redzic@hsc.edu.kw
Hasan
Fuad A
FA
Al-Sarraf
Hameed
H
D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D033705:Equilibrative Nucleoside Transport Proteins / Q000235:genetics*; D005753:Gastric Mucosa / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D009853:Omeprazole / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
D033705:Equilibrative Nucleoside Transport Proteins; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; C065171:cif nucleoside transporter; D000241:Adenosine; D009853:Omeprazole