Exogenous leptin inhibits the secretion of pancreatic juice via a duodenal CCK1-vagal-dependent mechanism in anaesthetized rats.
Leptin originally described as product of the ob gene has been shown to be expressed in various tissues including the gastrointestinal tract. In this study, we investigated the influence of leptin on the secretion of pancreatic juice in biliary-pancreatic duct cannulated anaesthetised rats and in dispersed rat pancreatic acini in vitro. Exogenous leptin was given in boluses intravenously with or without CCK-8 (12 pmol kg(-1) body weight) in the presence or absence pharmacological CCK(1) receptor blockade, cervical vagotomy, and capsaicin pre-treatment. Administration of leptin (0.1, 1 and 10 microg kg(-1) body weight) did not affect the volume of bile and pancreatic juice while the protein and trypsin outputs were reduced in a dose-dependent manner. In the rats, leptin inhibited CCK-8 stimulated protein and trypsin outputs stronger than the basal pancreatic secretion. The inhibition by leptin was abolished by the pharmacological CCK(1) receptor blockade, cervical vagotomy, and capsaicin pre-treatment. In contrast, leptin did not affect basal and CCK-8-stimulated amylase release from the dispersed rat pancreatic acini in vitro. In conclusion, the results of the present study suggest that leptin does not act directly on the rat pancreatic acinar cells but inhibits the secretion of pancreatic enzymes acting indirectly via a neurohormonal CCK-vagal-dependent mechanism.
Matyjek
R
R
The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, 05-110 Jablonna, Poland.
Herzig
K-H
KH
Kato
S
S
Zabielski
R
R
D000681:Amylases / Q000378:metabolism; D000758:Anesthesia; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D004386:Duodenum / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D007262:Infusions, Intravenous; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D010189:Pancreatic Juice / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D043886:Receptor, Cholecystokinin A / Q000037:antagonists & inhibitors* / Q000502:physiology; D012844:Sincalide / Q000494:pharmacology; D014357:Trypsin / Q000378:metabolism; D014628:Vagotomy; D014630:Vagus Nerve / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D020738:Leptin; D043886:Receptor, Cholecystokinin A; D000681:Amylases; D014357:Trypsin; D012844:Sincalide; D002211:Capsaicin