Influence of adenosine receptors on the development of caerulein-induced acute pancreatitis.
Acute pancreatitis leads to hypoxia caused by vasoconstriction and to activation of lysosomal and digestive enzymes resulting in pancreas autodigestion and damage. This causes activation of leucocytes and increased expression of adhesive molecules enabling margination and adhesion of activated leucocytes to the endothelium. Activated leucocytes are the source of proinflammatory cytokins and oxygen-free radicals which intensify the inflammatory response. The reports indicating that adenosine may prevent activation of the above-mentioned processes in ischaemia prompted us to undertake this study. The study was performed in two stages. The first stage was to evaluate the effects of agonists and antagonists of adenosine receptors on normal pancreas while the second one was to determine the influence of these substances on the development of caerulein-induced acute pancreatitis. During the first stage, the animals were injected intraperitoneally with the substances examined: the A1 receptor antagonist--DPCPX, the A2 receptor agonist--CGS 21680, the A2 receptor antagonist--ZM 241385 and the A3 receptor agonist--IB-MECA and then received intravenous saline. The control animals were subjected only to the 12 h intravenous infusion of 0.15 M NaCl. During the second stage, after the intraperitoneal administration of adenosine receptor agonists and antagonists (as in the first stage), acute pancreatitis was induced with the 12 h intravenous infusion of 5 micrograms/kg/h caerulein. Identical acute pancreatitis was induced in the control animals, however no other substances were administered. The pancreatic tissue samples were collected directly after intravenous infusion. The severity of inflammatory processes in the pancreas was evaluated on the basis of the plasma amylase activity, pancreatic weight and enhancement of histopathological changes observed in this organ. In the animals infused with saline alone, no effects of the substances examined on the pancreatic weight, plasma amylase activity and histopathological features were observed. The intravenous caerulein infusion induced acute pancreatitis expressed as bigger pancreatic weight, increased plasma amylase activity and tissue damage (oedema, cell vacuolization, leucocyte infiltration). The A2 receptor agonist administration preceding the induction of acute pancreatitis decreased the pancreas damage caused by caerulein. Lower weight of the pancreas and decreased plasma amylase activities were observed; on histopathological examination--oedema, leucocyte infiltration and intensity of alveolar cell vacuolization were lower. On the other hand, intraperitoneal pretreatment with the A2 receptor antagonist intensified the pancreas injury. The A1 receptor blockade and A3 receptor stimulation in the animals injected with caerulein did not affect the pancreatic weight, plasma amylase activity or histopathological picture of the organ. The administration of A2 receptor agonists decreases the organ injury in caerulein-induced acute pancreatitis in rats. This action may result from modulating effects of these substances on different stages of the cascade of inflammatory reactions. However, the present study did not reveal any effect of the A1 receptor agonist or A3 receptor antagonist on inflammatory processes in the experimental model described.
Szczerbiński
Mariusz
M
Department of Gastroenterology, Medical University of Lublin.
Celiński
Krzysztof
K
Słomka
Maria
M
Kasztelan-Szczerbińska
Beata
B
Cichoz-Lach
Halina
H
D000208:Acute Disease; D000241:Adenosine / Q000502:physiology; D000818:Animals; D002108:Ceruletide; D008297:Male; D010195:Pancreatitis / Q000139:chemically induced / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000502:physiology*
D018047:Receptors, Purinergic P1; D002108:Ceruletide; D000241:Adenosine