title: Dual, time-dependent deleterious and protective effect of anandamide on the course of cerulein-induced acute pancreatitis. Role of sensory nerves.
abstract: Some recent studies indicate that cannabis may induce acute pancreatitis in humans and administration of anandamide increases the severity of acute pancreatitis; whereas another study exhibits some therapeutic effects in acute pancreatitis. Aim of the present study was to discover what is the reason for these opposite confusing results and to determine the role of sensory nerves in this effect. Acute pancreatitis was induced in rats by cerulein. Anandamide, an endogenous cannabinoid, was administered i.p. (1.5 micromol/kg) before or 2 h after cerulein administration. Stimulation of sensory nerves was performed by capsaicin (0.5 mg/kg s.c.). In rats treated with combination of anandamide plus capsaicin, capsaicin was given 10 min after each dose of anandamide. After the last injection of cerulein or 4 h later, the study was terminated. In our study we observed that stimulation of sensory nerves by capsaicin, before administration of cerulein, reduced the severity of acute pancreatitis. Anandamide, administered alone before cerulein, increased pancreatic damage in acute pancreatitis. Anandamide administered in combination with capsaicin, before cerulein, abolished the capsaicin-induced protective effect on the pancreas. Opposite effects were observed when capsaicin and anandamide were administered after injection of cerulein. Capsaicin increased the severity of acute pancreatitis, whereas anandamide reduced pancreatic damage and reversed the deleterious effect of capsaicin. We conclude that the effect of anandamide on the severity of acute pancreatitis depends on the phase of this disease. Administration of anandamide, before induction of pancreatitis, aggravates pancreatic damage; whereas anandamide administered after induction of pancreatitis, reduces the severity of acute pancreatitis. Sensory nerves are involved in the mechanism of this biphasic effect of anandamide.
authors.affiliation: Department of Physiology, Jagiellonian University Medical College, Krakow, Poland. mpdembin@cyf-kr.edu.pl
authors.forename: Artur
authors.initials: A
authors.lastname: Dembiński
authors.forename: Zygmunt
authors.initials: Z
authors.lastname: Warzecha
authors.forename: Piotr
authors.initials: P
authors.lastname: Ceranowicz
authors.forename: Anna M
authors.initials: AM
authors.lastname: Warzecha
authors.forename: Wiesław W
authors.initials: WW
authors.lastname: Pawlik
authors.forename: Marcin
authors.initials: M
authors.lastname: Dembiński
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Rembiasz
authors.forename: Paweł
authors.initials: P
authors.lastname: Sendur
authors.forename: Beata
authors.initials: B
authors.lastname: Kuśnierz-Cabala
authors.forename: Romana
authors.initials: R
authors.lastname: Tomaszewska
authors.forename: Eve
authors.initials: E
authors.lastname: Chowaniec
authors.forename: Peter C
authors.initials: PC
authors.lastname: Konturek
mesh_terms: D000208:Acute Disease; D000818:Animals; D001095:Arachidonic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D063385:Cannabinoid Receptor Modulators / Q000008:administration & dosage / Q000494:pharmacology*; D002108:Ceruletide / Q000633:toxicity; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D063388:Endocannabinoids; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy*; D053284:Polyunsaturated Alkamides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D002108:Ceruletide; C078814:anandamide