Role of endogenous melatonin and its MT2 receptor in the modulation of caerulein-induced pancreatitis in the rat.
The present study investigated the involvement of endogenous melatonin in the prevention of pancreatic damage provoked by caerulein-induced pancreatitis (CIP) by using the luzindole, the antagonist of melatonin MT2 receptors. CIP was produced by subcutaneous infusion of caerulein to conscious rats (25 microg/kg). Luzindole (1, 2 or 4 mg/kg) was given as an intraperitoneal bolus injection 30 min prior to the start of CIP. Lipid peroxidation products, malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) were measured in the pancreas by LPO-584 commercial kit. CIP was confirmed by histological examination and manifested by significant increases of plasma activities of amylase, lipase and tumor necrosis factor alpha (TNFalpha) (by 500%, 1000% and 600%, respectively) comparing to the control values. This was accompanied by a 40% limitation in pancreatic blood flow (PBF) and by 200% increase of MDA+4-HNE in the pancreas of CIP rats. Administration of luzindole to the CIP rats reduced PBF, aggravated the histological manifestations of pancreatitis, resulted in the significant augmentation of pancreatic MDA + 4-HNE content, and produced the marked increases of plasma levels of lipase, amylase and TNFalpha, comparing to the values observes in the rats with CIP alone. These results suggest that endogenous melatonin through its receptor MT2 plays an important role in the attenuation of pancreatic damage produced by overstimulation with caerulein.
Jaworek
J
J
Chair of Physiology, Jagiellonian University School of Medicine, Kraków, Poland.
Konturek
S J
SJ
Leja-Szpak
A
A
Nawrot
K
K
Bonior
J
J
Tomaszewska
R
R
Stachura
J
J
Pawlik
W W
WW
D000681:Amylases / Q000097:blood; D000818:Animals; D002108:Ceruletide; D004305:Dose-Response Relationship, Drug; D008049:Lipase / Q000097:blood; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D008550:Melatonin / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D010179:Pancreas / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology*; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors*; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors*; D044094:Receptors, Melatonin; D014363:Tryptamines / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D044094:Receptors, Melatonin; D014363:Tryptamines; D014409:Tumor Necrosis Factor-alpha; C057154:luzindole; D002108:Ceruletide; D008049:Lipase; D000681:Amylases; D008550:Melatonin