Haemodynamic and Exocrine Effects of Caerulein at Submaximal and Supramaximal Levels on the Rat Pancreas: Role of Cholecystokinin Receptor Subtypes

Background: We have investigated the involvement of cholecystokinin (CCK) receptor subtypes in haemodynamic changes in the pancreas of anaesthetized rats during submaximal and supramaximal stimulation with the CCK analogue, caerulein. Methods: For submaximal stimulation, caerulein (0.4 nmol/kg/h) was infused intravenously, while acute pancreatitis was induced by intraperitoneal injections of high doses of caerulein (3 x 25 nmol/kg). Pancreatic blood flow was measured by hydrogen clearance.Results: Low caerulein doses increased pancreatic blood flow by 26 8 8% and vascular conductance by 24 8 4%. This effect was mimicked by the CCK2 agonist gastrin-17. All effects were abolished by a CCK2 antagonist while a CCK1 antagonist remained inactive. Conversely, amylase output by caerulein was abolished by CCK1 receptor blockade, but not by inhibition of CCK2 receptors. During caerulein-induced pancreatitis, vascular conductance increased by 109 8 26% and remained elevated throughout the experiment; vascular flow initially increased by 62 8 27% and then returned to baseline. The vascular effects were prevented by a CCK2 receptor antagonist, while the induction of pancreatitis was due to CCK-! receptor stimulation.Conclusions: Caerulein increases pancreatic vascular flow via activation of CCK2 receptors. This effect occurs both at submaximal and at supramaximal levels of exocrine stimulation.