Evidence for altered cellular calcium in the pathogenetic mechanism of acute pancreatitis in rats.
Although several pathophysiological sequences, such as protease activation, free radical generation, and inflammatory mediator release, have been described in acute pancreatitis, the precise mechanism by which acute pancreatitis is initiated is unknown. Cellular calcium, a key physiological signaling element in cell function and also a crucial pathological intracellular messenger in cell injury, appears to be involved in the initiation and development of acute pancreatitis. The present study provides several lines of evidence supporting this suggestion. First, verapamil (a calcium channel blocker) administration was associated with a significant protection of rats from acute pancreatitis induced by high doses of cerulein (50 micrograms/kg/hr, subcutaneously), as evidenced both histologically and biochemically. Second, verapamil was found to minimize the increased tissue levels of calcium, platelet-activating factor, and thromboxane B2 detected during acute pancreatitis. Third, acute pancreatitis could be observed in rats with elevated serum calcium levels at low doses of cerulein (5 micrograms/kg/hr, subcutaneously), but could not be observed in rats with normal serum calcium levels treated with low doses of cerulein. It is proposed that cellular calcium, which is a critical signaling component in the synthesis and release of inflammatory mediators and several other events, may be an important factor in the pathogenesis of cerulein-induced acute pancreatitis.
Zhou
W
W
Department of Biochemistry, University of Texas Health Science Center, San Antonio 78284, USA.
Shen
F
F
Miller
J E
JE
Han
Q
Q
Olson
M S
MS
D000208:Acute Disease; D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002108:Ceruletide / Q000494:pharmacology; D004357:Drug Synergism; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D010972:Platelet Activating Factor / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013929:Thromboxane B2 / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D010972:Platelet Activating Factor; D013929:Thromboxane B2; D002108:Ceruletide; D014700:Verapamil; D002118:Calcium