A400 AGA ABSTRACTS GASTROENTEROLOGY, Vol. 108, No. 4

C}~GES OF THE V,~NCI~TIC CELLUL;LR ME~:Bha~

Ca2+-Mg2+-ATPase ACTIVITY ~q ~TS WITH ACUTE PANCREA-

T ITIS ~ND TET~,IETHYLPY~AINE INFLUENCE

WMYG XP,YU~ YZ,XU JY.Dept of Gastroenterology, Hui JAn Hospital,Shanghai Second Medical University

To evaluate the changes o£ pancreatic cellular memorane Ca2~-Mg2+-~TPase activity in acute pancreati~ tis(AP) in race,and the correlation between Ca2+-Eg2+ -~TPase activity and MD,~,Ca2+ con~enz or amylase activity.Based upon these,the inf3aence of ~e~r~ethy -ipyrazine(TM~) on them was studied.

aP model in rats was induced by injection o£ 5% sodium taaroeholate into pancreatic dact.0a2~-Mg2+- ATPase activity was deter~ine~ by using PalaEoor's method.all rats were divided into three groaps:ehu~ operation,AP ~ntreated mad iW treated by T~,~.

a~ 6 ho~rs a£ter operation ,Ca2+-Mg2+-ATPase activity decreased,pancreatic tissue Ca2+,MDA con~en~ and amylase activit S increased signiEicantly in ~C~ untrea,ted group,as compared with in AP ~rea~ed with TEP.USing linear correlation analysis~it was found that there was e~rongly negative correlation between Ca2+-Mg2+-ATPase activity ann MD~ conten~,Ca2+ co~en~| or ~mylaee activity.All o£ these changes were prev ente~ by TMP.

Decreased pancreatic cellular membrane Ca2+-Mg2+- ~TPase activity in acute pancreatitis in ra~s might be caasea by lipidperoxidation reaction,which contri-

bute to intracellular Ca2+-over1~ad and amylase over- released.T~E showed it's benifical effects on the preservation of Ca2+~g2+-ATPase activity.

DISORDERED CALCIUM HOMEOSTASIS IN EXPERIMENTAL PANCREATITIS. J. B. Ward, R. Sutton, S. A. Jenkins, O. H. Petemen. Department of Surgery and the Physiological Laboratory, University of Liverpool, England, U. K.

The pathogenesis of acute pancreatitis is poorly understood but disruption of stimulus-secretion coupling may be an important event. As calcium is a key signal in this process we have examined acinar cell cytosolic calcium (Ca2+i) signalling in early experimentalpancreatitis.

Mice received hourly injections of caerulein (50/~g/kg) or saline. Pancreatic tissue was harvested after injections 1, 3, 5 and'7. Acini were isolated by collagenase digestion, loaded with fura-2, and : intracellular calcium responses to acetylcholine (100nM ACh) studied using digital-imaging mierofiuorimetry. Two sets of experiments were performed at each stage.

The number of cells demonstrating a normal oscillatory response of :.. [Ca2+i] to 100riM ACh diminished progressively: 20 of 24, 18 of 20, 5 of 14, 2 of 8 after 1, 3, 5 and 7 injections of caerulein respectively (X2r,,d=15.09, p<0.001). In controls the proportion of cells demonstrating a normal oscillatory response remained high, notably after injections 5 (38 of 43, vs caerulein: X2y=13.07, p<0.001) and 7 (29 of 30, vs eaerulein: X2y=17.14, p<0 001) These results indicate that there is Progressive disturbance'of acinar cell calcium:homeostasis with repeated injections of caerulei n. Further work is required to 'assess the significance of disordered calcium homeostasis in the pathogenesis of acute pancreatitis.

Wassef, W., Boyd, J., Foxx-Omstein, A., Sessler, C., Fowler, B., Zfass, A.M., Everette, S. The Role of ICAM-1 in Predicting the Severity of Acute Pancreatitis. Divisions of Gastroenterology and Pulmonary Medicine, Medical College of VirginiaJVCU, Richmond, VA

Intercellular Adhesion Molecules-1 (ICAM-1), a glycoprotein adhesion receptor found on the surface of endothelial cell, is constitutively expressed at low levels. High levels of it are found in circulating blood of patients with sepsis and other inflammatory conditions, due to up-regulation and shedding. We hypothesized that the ICAM-1 levels may be elevated in patients with acute pancreatitis, particularly in severe cases, due to the release of pro-inflammatory mediators.

In order to determine the relationship between ICAM-1 level and the severity of pancreatitis, serum was obtained from patients at the time of admission to the hospital with acute pancreatitis. Patients in the' study group were further evaluated by determining a Glasgow score as a measure of the severity of the pancreatitis. Results: 25 patients with pancreatitis were studied (13 males, 12 females). The mean age of the study group was 35. The etiology of the pancreatitis was variable: 15-alcohol, 4-gallstones, 2-meds, 1-hereditary, 1- hyperealcemia, 1-hypertriglyceridemia, and 1-trauma. 9 bealthyvolunteers served as controls. They had comparable age and sex distribution to the study population. The median value of sICAM-1 in control patients was 353.88+/-53.95ng/ml. The median value of sICAM-I in patients with mild pancreatitis as defined by Glasgow scale of 0(n=8), l(n=10), or 2(n=5) was 446.63+/- 46.21ng/ml. This was not significantly different from the control group (p=0.112). However, the median value of sICAM-1 in patients with severe pancreatitis as predicted by a Glasgow score of greater than or equal to 3(n=2) was 945+/- 221 ng/ml. This was significantly different from the control group (p=0.003) Furthermore, using logistic regression analysis, the serum value of ICAM-1 increased with the severity of the pancreatitis, as evaluated by the Glasgow scale (p=0.0174). Conclusion: Patients with severe pancreatitis tend to have higher ICAM-1 levels. ICAM-I may prove to be a useful early serum marker for severe pancreatitis, further study is needed.

CENTRALLY MEDIATED PANCREATIC :SECRETION IS STIMULATED THROUGH THE Y1 RECEPTOR :AND INHIBITED THROUGH THE Y2 RECEPTOR. DC Whitcomb. M Yin, JT Curtis, AM Puccio, J Reeve a n d A F Sved. Depts of Medicine and Neuroscience, Univ. Pittsburgh, Pittsburgh, PA 15261.

Pancreatic secretion regulated by complex neurohormonal mech- anisms that may be coordinated in the dorsal vagal complex (DVC). Systemic infusion of PYY inhibits centrally stimulated pancreatic: secretion, however microinjection of 10 pmol PYY into the NTS stimu- lates pancreatic secretion. Aim: To determine the receptor subtype and dose response characteristics of the DVC - coordinated pancre- atic response to PYY. Methods: Fasted rats were urethane anes- thetized and prepared with pancreatic duct and bile duct cannulas, venous and arterial catheters for monitoring Cardiovascular response, and mounted on a stere'otaxic frame for microinjection studies. After 1 hour, basal pancreatic secretion was measured and 100 nl injec- tions were made into the NTS, DMV or adjacent areas. We tested NPY, PYY, PYY(3-36) and PYY(Pro34) in amounts of 0, 0.1, 1, 10 and 100 pmol while measuring cardiovascular and pancreatic re- sponses. Results: PYY stimulated pancreatic fluid and Protein secretion when injected into the NTS at 1.0 and 10 pmol but had no apparent effect at 100 pmol. Control injections (buffer) or injections lateral to the NTS were without effect on pancreatic or cardiovascular function. PYY(3-36) (Y2 receptor agonist), had no stimulatory effect on pancreatic fluid or protein secretion, and was inhibitory at higher concentrations. However, PYY(pro34); a Y1 agonist, stimulated pancreatic fluid and protein secretion in a dose-dependent manner. NPY caused a decrease in pancreatic fluid volume with an increases in protein output similar to PYY. NPY had a greater effect than PYY on heart rate and blood pressure. Conclusions: The stimulatory effects of small doses of centrally administered PYY in the anesthetized rat are mediated by the Y1 receptor. However, as the dose Of PYY increases, the inhibitory effect.of the Y2 receptor prevails. Thus, central modulation of pancreatic secretion by PYY is complex, dose-dependent and represents an interplay of the effects of Y1 and Y2, and possibly other receptors. NPY appears to affect pancreatic fluid and protein secretion in a nonparallel manner. (Supported by NIH R29 DK45781 to Dr. Whitcomb)