Modulation of exocrine pancreatic secretion by leptin through CCK(1)-receptors and afferent vagal fibres in the rat.
In this report, we determined whether leptin could modify the exocrine pancreatic secretion of anaesthetized rats in vivo. Intravenous injection of recombinant murine leptin resulted in a time- and dose-dependent stimulation of exocrine pancreatic secretion, maximally observed with 30 nmol/kg of leptin. This stimulation of pancreatic water, bicarbonate, and protein output was abolished by atropine, hexamethonium, L364,718 ([3S(-)-N-(1,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepine]), a cholecystokinin CCK(1) receptor antagonist or perivagal capsaicin pretreatment, but unaffected by the CCK(2) receptor antagonist L365,260 ([3R(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3yl)-N'-(3-methylphenyl)urea]). In addition, the physiological dose of 3 nmol/kg leptin, ineffective per se, potentiated the secretory effect of 45 pmol/kg of cholecystokinin octapeptide (CCK-8) on exocrine pancreatic secretion. Furthermore, intraperitoneal leptin induced a rapid increase in plasma CCK levels in vivo in the rat. In conclusion, exogenous leptin can modulate exocrine pancreatic secretion through mechanisms involving CCK(1) receptors and capsaicin-sensitive afferent fibres in the rat. Whether this may have a physiological relevance in the postprandial regulation of exocrine pancreatic secretion and thus in nutrient digestion will require further investigations.
Guilmeau
Sandra
S
Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 410, IFR 02 Claude Bernard, Faculté de Médecine Xavier Bichat, 16 Rue H. Huchard, BP 416, 75870 Cedex 18, Paris, France.
Nagain-Domaine
Claire
C
Buyse
Marion
M
Tsocas
Annick
A
Rozé
Claude
C
Bado
André
A
D000344:Afferent Pathways / Q000502:physiology*; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D002766:Cholecystokinin / Q000097:blood; D020738:Leptin / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D009412:Nerve Fibers / Q000502:physiology*; D010179:Pancreas / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D014630:Vagus Nerve / Q000502:physiology* / Q000648:ultrastructure
D020738:Leptin; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin; D011994:Recombinant Proteins; D002766:Cholecystokinin; D002211:Capsaicin