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

Abstract

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 × 25 nmol/kg). Pancreatic blood flow was measured by hydrogen clearance. Results: Low caerulein doses increased pancreatic blood flow by 26 ± 8% and vascular conductance by 24 ± 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 ± 26% and remained elevated throughout the experiment; vascular flow initially increased by 62 ± 27% and then returned to baseline. The vascular effects were prevented by a CCK₂ receptor antagonist, while the induction of pancreatitis was due to CCK₁ 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.