title: Involvement of vagal nerves in the pancreatostimulatory effects of luminal melatonin, or its precursor L-tryptophan. Study in the rats.
abstract: Melatonin, known as a product of pineal gland is also produced in the digestive system. Melatonin receptors have been detected on pancreatic beta cells and this indoloamine influences the endocrine pancreatic function but the role of melatonin on pancreatic exocrine secretion is not known.
  
  
  OBJECTIVE
  To evaluate the effects of intraduodenal administration of melatonin or its precursor L-tryptophan on pancreatic protein output under basal conditions or following the stimulation of exocrine pancreas with diversion of pancreato-bliliary juice (DBPJ) and to assess the involvement of vagal nerves, and CCK in this process.
  
  
  METHODS
  Under pentobarbiturate anesthesia the Wistar rats weighting 300g were 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 to the rats as intraduodenal (i.d.) bolus injection. Bilateral vagotomy was performed in the group of animals 7 days before the experiment. To assess the role of CCK in the melatonin or L-tryptophan-induced pancreatic secretory functions, lorglumide, the CCK(1) receptor antagonist was administered at dose of 1 mg/kg i.d. 15 minutes before the application of examine substances. During the study samples of pancreato-biliary juice were collected in 15 minutes aliquots to measure the protein outputs.
  
  
  RESULTS
  Melatonin (1, 5, or 25 mg/kg ) or L-tryptophan (10, 50 or 250 mg/kg) produced significant and dose-dependent increases in pancreatic protein secretion under basal conditions or following the stimulation of this secretion by DBPJ. This was accompanied by a dose-dependent rise in CCK plasma level. Stimulation of pancreatic protein outputs caused by melatonin or L-tryptophan was completely abolished by vagotomy, or pretreatment with lorglumide. We conclude that melatonin as well as its precursor L-tryptophan, stimulates pancreatic exocrine function via mechanisms involving enteropancreatic reflexes and CCK.
authors.affiliation: Department of Med Physiology, Faculty of Health Sciences, Jagiellonian University Medical College, 16 Grzegorzecka Street, Kraków, Poland. mpjawore@cyf-kr.edu.pl
authors.forename: K
authors.initials: K
authors.lastname: Nawrot-Porabka
authors.forename: J
authors.initials: J
authors.lastname: Jaworek
authors.forename: A
authors.initials: A
authors.lastname: Leja-Szpak
authors.forename: J
authors.initials: J
authors.lastname: Szklarczyk
authors.forename: M
authors.initials: M
authors.lastname: Kot
authors.forename: M
authors.initials: M
authors.lastname: Mitis-Musioł
authors.forename: S J
authors.initials: SJ
authors.lastname: Konturek
authors.forename: W W
authors.initials: WW
authors.lastname: Pawlik
mesh_terms: D000818:Animals; D002766:Cholecystokinin / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D046790:Pancreas, Exocrine / Q000187:drug effects* / Q000378:metabolism; D010189:Pancreatic Juice / Q000378:metabolism; D011377:Proglumide / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043886:Receptor, Cholecystokinin A / Q000037:antagonists & inhibitors / Q000502:physiology; D014364:Tryptophan / Q000097:blood / Q000494:pharmacology*; D014628:Vagotomy; D014630:Vagus Nerve / Q000187:drug effects* / Q000502:physiology
chemical_list: D043886:Receptor, Cholecystokinin A; D014364:Tryptophan; D002766:Cholecystokinin; D011377:Proglumide; D008550:Melatonin; C048181:lorglumide