Effect of adenosine and adenosine agonists on amylase release from rat pancreatic lobules

The effects of adenosine on the amylase secretion from rat pancreatic lobules have been studied. Adenosine induces a dose-dependent stimulation on amylase release, which is maximal at a concentration of 10(-4) M. It has been observed a clear inhibition of this secretory action when atropine was added whereas no amylase release was seen in isolated acini after adenosine. The effect of adenosine is completely blocked by the adenosine receptors antagonist theophylline (10(-4) M), but not by dipyridamole (10(-3) M), a drug that inhibits the transport of adenosine into the cell. The increase of amylase secretion induced by adenosine is inhibited by either the relatively selective A1 receptor antagonist PD116,948 (10(-6) M) and by the A2 receptor antagonist PD115,199 (10(-6) M). Significant increases of amylase release are observed after the relatively selective A1 receptor agonist R-PIA (10(-5) M) and after the relatively selective A2 receptor agonist NECA (10(-4) M). Finally, the effect of R-PIA is not modified by coincubation with PD115,199 and the effect of NECA is not affected by coincubation with PD116,948. These results suggest that the action of adenosine is mediated through the release of acetylcholine and probably by the simultaneous occupation of both A1 and A2 adenosine receptors, whereas the intracellular action of adenosine could be discarded.