Endogenous adenosine modulates gastric acid secretion to histamine in canine parietal cells.
We have recently demonstrated the presence of A1 adenosine receptors on canine parietal cells which are involved in the inhibition of histamine-stimulated acid secretion. In order to demonstrate the importance of endogenously generated adenosine on acid secretion we examined the effect of compounds that either increase or decrease the availability of adenosine to the A1 receptor on histamine-stimulated parietal cell aminopyrine (AP) accumulation. Inclusion of 10 microM 8-phenyltheophylline, an adenosine receptor antagonist, with the cells resulted in a 35 +/- 12% and 31 +/- 9% increase in parietal cell AP accumulation at histamine concentrations of 1 microM and 10 microM, respectively. The effect of 8-phenyltheophylline was specific to histamine in that it did not affect carbachol-stimulated AP accumulation or dibutyryl cyclic AMP-stimulated AP accumulation. Inclusion of 1 microM dipyridamole, an inhibitor of adenosine transport, resulted in a 34 +/- 6% and 31 +/- 5% decrease in parietal cell AP accumulation at histamine concentrations of 1 microM and 10 microM, respectively. Again the effect of dipyridamole was specific to histamine in that it did not affect either carbachol- or dibutyryl cyclic AMP-stimulated AP accumulation. The addition of adenosine deaminase, 500 mU/ml, resulted in an enhanced histamine-stimulated AP accumulation at all the histamine concentrations. The effect was specific to histamine because the enzyme had no effect on either carbachol- or dibutyryl cyclic AMP-stimulated AP uptake. Our present data suggest that endogenous adenosine generated by the gastric cells can interact with parietal cell adenosine receptors to modulate acid secretion to histamine.(ABSTRACT TRUNCATED AT 250 WORDS)
Gerber
J G
JG
Division of Clinical Pharmacology, University of Colorado Health Sciences Center, Denver.
Payne
N A
NA
D000241:Adenosine / Q000502:physiology*; D000243:Adenosine Deaminase / Q000378:metabolism; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004176:Dipyridamole / Q000494:pharmacology; D004285:Dogs; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology*; D008297:Male; D010295:Parietal Cells, Gastric / Q000378:metabolism*; D011983:Receptors, Purinergic / Q000378:metabolism*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D011983:Receptors, Purinergic; D003994:Bucladesine; D004176:Dipyridamole; D006632:Histamine; D002217:Carbachol; D013806:Theophylline; C028322:8-phenyltheophylline; D000243:Adenosine Deaminase; D000241:Adenosine