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% 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.
Griesbacher
Thomas
T
Institute for Experimental and Clinical Pharmacology, Medical University of Graz, Graz, Austria. thomas.griesbacher@meduni-graz.at
Rainer
Irmgard
I
Heinemann
Akos
A
Groisman
Diana
D
D000818:Animals; D065094:Bradykinin B2 Receptor Antagonists; D002108:Ceruletide / Q000494:pharmacology*; D005260:Female; D005755:Gastrins / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D046790:Pancreas, Exocrine / Q000098:blood supply / Q000187:drug effects*; D010195:Pancreatitis / Q000139:chemically induced / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043886:Receptor, Cholecystokinin A / Q000819:agonists / Q000037:antagonists & inhibitors; D043887:Receptor, Cholecystokinin B / Q000819:agonists / Q000037:antagonists & inhibitors; D011949:Receptors, Cholecystokinin / Q000187:drug effects / Q000378:metabolism*; D012039:Regional Blood Flow / Q000187:drug effects; D013268:Stimulation, Chemical
D065094:Bradykinin B2 Receptor Antagonists; D005755:Gastrins; D007211:Indoles; C102662:PD 140548; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D002108:Ceruletide