Gerber J G, Payne N A
Division of Clinical Pharmacology, University of Colorado Health Sciences Center, Denver.
J Pharmacol Exp Ther. 1988 Jan;244(1):190-4.
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)
我们最近证实犬壁细胞上存在A1腺苷受体，其参与抑制组胺刺激的胃酸分泌。为了证明内源性生成的腺苷对胃酸分泌的重要性，我们研究了增加或减少腺苷与A1受体结合的化合物对组胺刺激的壁细胞氨基比林（AP）摄取的影响。在细胞中加入10微摩尔8-苯基茶碱（一种腺苷受体拮抗剂）后，在组胺浓度为1微摩尔和10微摩尔时，壁细胞AP摄取分别增加了35±12%和31±9%。8-苯基茶碱的作用对组胺具有特异性，因为它不影响卡巴胆碱刺激的AP摄取或二丁酰环磷酸腺苷刺激的AP摄取。加入1微摩尔双嘧达莫（一种腺苷转运抑制剂）后，在组胺浓度为1微摩尔和10微摩尔时，壁细胞AP摄取分别减少了34±6%和31±5%。同样，双嘧达莫的作用对组胺具有特异性，因为它不影响卡巴胆碱或二丁酰环磷酸腺苷刺激的AP摄取。加入500毫单位/毫升腺苷脱氨酶后，在所有组胺浓度下，组胺刺激的AP摄取均增强。该作用对组胺具有特异性，因为该酶对卡巴胆碱或二丁酰环磷酸腺苷刺激的AP摄取均无影响。我们目前的数据表明，胃细胞产生的内源性腺苷可与壁细胞腺苷受体相互作用，调节对组胺的胃酸分泌。（摘要截短至250字）
