Direct and indirect stimulation of pancreatic exocrine secretion by neurotensin in anaesthetized dogs.
1. The effects of neurotensin on pancreatic exocrine secretion were investigated both in the intact whole pancreas and in the isolated, blood-perfused pancreas ex vivo in anaesthetized dogs. 2. Intravenous (i.v.) injections of neurotensin (0.01-1 nmol/kg) elicited dose-dependent increases in the secretory rate of pancreatic juice without changes in plasma levels of cholecystokinin (CCK). The concentration of bicarbonate in the pancreatic juice induced by neurotensin was increased, but the protein concentration was scarcely changed. 3. The neurotensin-induced secretion was inhibited by SCH23390, a dopamine D-1 antagonist, but not by domperidone, phentolamine, propranolol, atropine, cimetidine, or L-364,718, a CCK antagonist. 4. Intra-arterial (i.a.) injections of neurotensin (0.1-3 nmol/kg) also elicited dose-dependent increases in the secretory rate of pancreatic juice flow, but did not change bicarbonate or protein concentration. The secretory activities were less effective and 1 nmol/kg of neurotensin i.a. was approximately equal to that of 0.03 nmol/kg of neurotensin i.v. 5. These results suggest that neurotensin mainly stimulates pancreatic secretion by acting indirectly. Neurotensin-induced secretion is, at least in part, mediated by endogenously released dopamine which activates dopamine D-1 receptors on the pancreas. In addition to its indirect action, neurotensin has a weak direct action to stimulate pancreatic secretion.
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
K
K
Iwatsuki
A
A
Horiuchi
L M
LM
Ren
S
S
Chiba
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D002766:Cholecystokinin / Q000097:blood; D004285:Dogs; D005260:Female; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D008297:Male; D009496:Neurotensin / Q000494:pharmacology*; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D010189:Pancreatic Juice / Q000187:drug effects / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D013268:Stimulation, Chemical
D001639:Bicarbonates; D011506:Proteins; D009496:Neurotensin; D002766:Cholecystokinin