Cannabinoids in acute gastric damage and pancreatitis.
Recent studies have shown that stimulation of cannabinoid 1 (CB1) receptor reduces the area of ischemic myocardial necrosis and affects activity of the digestive tract. The aim of the present study was to check whether the administration of CB1 receptor agonist or antagonist affects the stress-induced gastric ulceration and development of edematous pancreatitis.


METHODS
Experiments were performed on rats. Gastric lesions were induced by water immersion and restrain stress (WRS). Acute pancreatitis was induced by cerulein. Prior to WRS or before and during cerulein administration, a natural endogenous ligand for CB1 receptor, anandamide was administered intraperitoneally at the dose of 0.8, 1.5 or 3.0 micromol/kg. A synthetic CB1 receptor antagonist, AM 251 (ALEXIS(R) Biochemicals) was administrated at the dose of 4 micromol/kg i.p. alone or in combination with anandamide at the dose of 1.5 micromol/kg.


RESULTS
Administration of anandamide reduced gastric lesions and this effect was associated with am increase in gastric mucosal blood flow and mucosal DNA synthesis; whereas serum level of pro-inflammatory interleukin-1 beta was reduced. Treatment with AM 251 aggravated gastric damage and reversed protective effect of anandamide administration. Opposite effect was observed in the pancreas. Administration of anandamide increased dose-dependently the severity of pancreatitis. In histological examination, we observed an increase in pancreatic edema and inflammatory infiltration. Also, treatment with anandamide augmented the pancreatitis-induced increase in serum level of lipase, amylase, poly-C ribonuclease, and pro-inflammatory interleukin-1 beta; whereas pancreatic DNA synthesis was reduced. Treatment with AM 251 reduced histological and biochemical signs of pancreatic damage and reversed deleterious effect of anandamide in cerulein-induced acute pancreatitis.


CONCLUSIONS
Activation of CB1 receptors evokes opposite effects in the stomach and pancreas: in the stomach, exhibits protective effect against stress-induced gastric mucosal lesions; whereas in the pancreas, increases the severity of cerulein-induced pancreatitis.
Dembiński
A
A
Department of Physiology, Jagiellonian University Medical College, Krakow, Poland. mpdembin@cyf-kr.edu.pl
Warzecha
Z
Z
Ceranowicz
P
P
Dembiński
M
M
Cieszkowski
J
J
Pawlik
W W
WW
Konturek
S J
SJ
Tomaszewska
R
R
Hładki
W
W
Konturek
P C
PC
D000208:Acute Disease; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D002186:Cannabinoids / Q000494:pharmacology*; D002108:Ceruletide; D004247:DNA / Q000096:biosynthesis; D063388:Endocannabinoids; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D053583:Interleukin-1beta / Q000145:classification; D008297:Male; D010179:Pancreas / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors; D012149:Restraint, Physical; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000378:metabolism; D013312:Stress, Physiological / Q000150:complications / Q000209:etiology / Q000378:metabolism
D001095:Arachidonic Acids; D002186:Cannabinoids; D063388:Endocannabinoids; D053583:Interleukin-1beta; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; C103505:AM 251; D002108:Ceruletide; D004247:DNA; C078814:anandamide