Effects of synthesized phosphodiesterase inhibitors, DM 9278 and HWA 285, on pancreatic exocrine secretion of the dog.

The effects of synthesized phosphodiesterase inhibitors, DM 9278 and HWA 285, on pancreatic exocrine secretion were investigated in isolated and blood-perfused canine pancreas. Close-arterial injections of DM 9278 (10-300 micrograms) and HWA 285 (300-3000 micrograms) caused dose-dependent increases in the flow rate of pancreatic juice and perfusion blood flow. Bicarbonate concentration in the pancreatic juice stimulated by DM 9278 (300 micrograms) or HWA 285 (3000 micrograms) was significantly higher than that in the resting pancreatic juice, although neither of the compounds affected protein concentrations in the pancreatic juice. In the secretory volume, 100 micrograms of DM 9278 corresponded roughly to 1000 micrograms of HWA 285, 0.1 units of secretin or 0.3 units of pancreozymin. These secretory and vascular effects were not modified by pretreatment with atropine or sulpiride. This study suggests that both DM 9278 and HWA 285 act directly on ductular cells of the pancreas and induce secretion of water and electrolytes.