Secretagogue-evoked time-course changes on pancreatic juice secretion in the anaesthetized rat

1. In the present time-course study, we have examined the interactions between the phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and the synthetic gut hormones, cholecystokinin-octapeptide (CCK-8) and secretin on pancreatic juice secretion in anaesthetized rat. 2. Administration of either TPA (10(-8) mol kg-1 hr-1), secretin (100 pmol kg-1 hr-1) or CCK-8 (150 pmol kg-1 hr-1) in the anaesthetized rat resulted in marked time-course increases in pancreatic juice flow, amylase secretion and total protein output compared to saline controls. The effect of secretin on juice flow was more pronounced and sustained compared to the smaller responses obtained with either CCK-8 or TPA. Similarly, CCK-8 evoked increases in protein output and amylase secretion compared to the responses obtained with either secretin or TPA. 3. Simultaneous infusion of TPA with either CCK-8 or secretin resulted in a marked reduction in pancreatic juice flow, total protein output and amylase secretion compared to the responses obtained with either CCK-8 or secretin alone. 4. Administration of polymyxin B (10(-8) mol kg-1 hr-1), a protein kinase C inhibitor with either TPA and CCK-8 or TPA and secretin caused a partial reduction of the inhibitory effect of TPA on CCK-8 and secretin-evoked secretory responses. 5. The present study further implicates the involvement of protein kinase C in the modulation of CCK-8 and secretin-induced pancreatic juice secretion in the anaesthetized rat.