Melatonin, considered as a main pineal product, may be also synthetized in the gastrointestinal tract from
L-tryptophan.
Melatonin has been recently shown to affect
insulin release and its receptors have been characterized in the pancreas however, the effects of
melatonin on the pancreatic
enzyme secretion have not been examined. The aim of this study was to investigate the effects of
melatonin or
L-tryptophan on
amylase secretion in vivo in anaesthetized rats with pancreato-
biliary fistulas, and in vitro using isolated pancreatic acini.
Melatonin (1, 5 or 25 mg/kg) or
L-tryptophan (10, 50 or 250 mg/kg) given to the rats as a intraperitoneal (i.p.) bolus injection produced significant and dose-dependent increases in pancreatic
amylase secretion under basal conditions or following stimulation of
enzyme secretion by diversion of bile-pancreatic juice. This was accompanied by a dose-dependent rise in
melatonin plasma level. Stimulation of pancreatic
enzyme secretion caused by
melatonin or
L-tryptophan was completely abolished by
vagotomy, deactivation of sensory nerves with
capsaicin or pretreatment with CCK1 receptor antagonists (
tarazepide or
L-364,718). Pretreatment with
luzindole, an antagonist of
melatonin MT(2) receptor failed to affect
melatonin- or
L-tryptophan-induced
amylase secretion. Administration of
melatonin (1, 5 or 25 mg/kg i.p.) or
L-tryptophan (10, 50 or 250 mg/kg i.p.) to the rats resulted in the dose-dependent increase of
cholecystokinin (CCK) plasma immunoreactivity.
Enzyme secretion from isolated pancreatic acini was not significantly affected by
melatonin or
L-tryptophan used at doses of 10(-8) -10(-5) M. We conclude that exogenous
melatonin, as well as that produced endogenously from
L-tryptophan, stimulates pancreatic
enzyme secretion in vivo while increasing CCK release. Stimulatory effect of
melatonin or
L-tryptophan on the exocrine pancreas involves vagal sensory nerves and the CCK release by these substances.