Modulation of pancreatic enzyme secretion by melatonin and its precursor; L-tryptophan. Role of CCK and afferent nerves.
Melatonin, a pineal hormone, is also produced in the gastrointestinal tract. Melatonin receptors have been detected in the stomach, intestine and pancreas. This indole inhibits insulin secretion but its role in the physiological modulation of exocrine pancreatic function is yet unknown. The aim of this study was to evaluate the pancreatic secretory effect of melatonin and its precursor; L-tryptophan given intraduodenally (i.d.) to the conscious rats with intact or capsaicin deactivated sensory nerves. CCK(1) receptor antagonist; tarazepide, was used in the part of the study to determine the involvement of CCK in the secretory effects of melatonin. The secretory studies were performed on awaken rats surgically equipped with silicone catheters, one of them was inserted into pancreato-biliary duct, the other one--into duodenum. Melatonin (1, 5 or 25 mg/kg) or L-tryptophan (10, 50 or 250 mg/kg) were administered i.d. Samples of pancreatic juice were collected in 15 minutes aliquots. Tarazepide (2,5 mg/kg i.p.) was given to the rats 15 min prior to the administration of melatonin or L-tryptophan. Neurotoxic dose of capsaicin (100 mg/kg s.c.) was used to deactivate afferent nerves and thus to assess the role of these nerves in the melatonin-induced pancreatic enzyme secretion. Administration of melatonin (1, 5 or 25 mg/kg i.d.) or L-tryptophan (10, 50 or 250 mg/kg i.d.) significantly increased pancreatic amylase outputs. Deactivation of sensory nerves by capsaicin or administration of CCK(1) - receptor antagonist; tarazepide, reversed the stimulatory effects of melatonin or L-tryptophan on pancreatic secretory function. Administration of melatonin or its amino-acid precursor to the rats resulted in the significant and dose-dependent rises of melatonin and CCK plasma levels. We conclude that melatonin or its precursor; L-tryptophan stimulates pancreatic enzyme secretion via stimulation of CCK release and activation of duodeno-pancreatic reflexes.
Leja-Szpak
A
A
Department Med Physiol Faculty of Health Care, Jagiellonian University Collegium Medicum, Cracow, Poland.
Jaworek
J
J
Nawrot-Porabka
K
K
Palonek
M
M
Mitis-Musioł
M
M
Dembiński
A
A
Konturek
S J
SJ
Pawlik
W W
WW
D000681:Amylases / Q000378:metabolism; D000818:Animals; D002766:Cholecystokinin / Q000502:physiology*; D008297:Male; D008550:Melatonin / Q000097:blood / Q000494:pharmacology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D010189:Pancreatic Juice / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014364:Tryptophan / Q000097:blood / Q000494:pharmacology*
D014364:Tryptophan; D002766:Cholecystokinin; D000681:Amylases; D008550:Melatonin