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 antagonis ts 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 A(2A) 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 nm ol/kg), a selective adenosine A(1) receptor agonist, did not cause the panc reatic secretion. CGS21680 (3-30 nmol/kg) and secretin (0.01-0.03 pmol/kg) increased the bicarbonate concentration in pancreatic juice and decreased t he protein concentration. CCK-8 (0.1-0.3 pmol/kg) increased the protein con centration but did not alter the bicarbonate concentration. DMPX (5-50 nmol /kg), a weak adenosine A(2A) receptor antagonist, caused a progressive para llel shift to the right in the dose-response curve for CGS21680-induced pan creatic secretion without changes in the maximal response. DPCPX (100 nmol/ kg), a selective A(1) adenosine receptor antagonist, did not antagonize the CGS21680-induced pancreatic secretion. Schild analysis of the data indicat ed that the apparent pA(2) value for DMPX was 8.3 using CGS21680 as the ago nist. The slope of the Schild regression line was not different from 1. Whe n a phosphodiesterase IV inhibitor rolipram (0.1 nmol/kg) was added, pancre atic 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 sugge st the existence of adenosine A(2A) receptors in the exocrine cells of the dog pancreas involved in the water and bicarbonate secretory response. (C) 2000 Editions scientifiques et medicales Elsevier SAS.