Subtypes of adenosine receptors on pancreatic exocrine secretion in anaesthetized dogs

Characterization of adenosine receptor subtypes was examined on the canine exocrine pancreas using selective adenosine receptor agonists and antagonists in the isolated and blood-perfused pancreas of anaesthetized dogs. Each drug was injected intra-arterially in a single bolus fashion. Graded doses of CGS21680 (1-300 nmol/kg), a selective adenosine A2A receptor agonist, produced dose-dependent increases in the secretory rate of pancreatic juice, with a maximum effect at approximately 30 nmol/kg. However, CPA (1-300 nmol/kg), a selective adenosine A1 receptor agonist, did not cause the pancreatic secretion. CGS21680 (3-30 nmol/kg) and secretin (0.01-0.03 pmol/kg) increased the bicarbonate concentration in pancreatic juice and decreased the protein concentration. CCK-8 (0.1-0.3 pmol/kg) increased the protein concentration but did not alter the bicarbonate concentration. DMPX (5-50 nmol/kg), a weak adenosine A2A receptor antagonist, caused a progressive parallel shift to the right in the dose response curve for CGS21680-induced pancreatic secretion without changes in the maximal response. DPCPX (100 nmol/kg), a selective A1 adenosine receptor antagonist, did not antagonize the CGS21680-induced pancreatic secretion. Schild analysis of the data indicated that the apparent pA2 value for DMPX was 8.3 using CGS21680 as the agonist. The slope of the Schild regression line was not different from 1. When a phosphodiesterase IV inhibitor rolipram (0.1 nmol/kg) was added, pancreatic secretion induced by CGS21680 (10 nmol/kg) and secretin (0.03 pmol/kg) were potentiated, but not that of CCK-8 (0.3 pmol/kg). These results suggest the existence of adenosine A2A receptors in the exocrine cells of the dog pancreas involved in the water and bicarbonate secretory response.