EFFECTS OF CHOLECYSTOKININ AND CARBACHOL ON MEMBRANE FLUIDITY IN PANCREATIC ACINI

The effects of pancreatic secretagogues on the membrane fluidity of pa ncreatic acini were investigated using rimethylammonium)phenyl]-6-phen yl-1,3-5-hexatriene iodide as a probe. Two kinds of pancreatic secreta gogues, one category of which induces acute pancreatitis (cholecystoki nin and carbachol) and another which does not induce acute pancreatiti s (bombesin, CCK-JMV-180, and secretin), as well as lecithin were used to investigate the effect of changes in membrane fluidity of acini. O ur study revealed that the membrane fluidity of the pancreatic acini w as unaffected by a physiological dose (10(-11) M) of cholecystokinin. However, stimulation with a supramaximal dose of cholecystokinin (10(- 8) M) increased membrane fluidity markedly within 20 min. Membrane flu idity increased dose-dependently with increasing CCK stimulation. A su pramaximal dose of cholecystokinin also induced bleb formation and inc reased LDH release. These phenomena were blocked by simultaneous incub ation with CR1505 (Loxiglumide), a potent antagonist of peripheral cho lecystokinin receptors. A supramaximal dose of carbachol (10(-3) M) al so induced increases in the membrane fluidity. Pancreatic secretagogue s that do not induce acute pancreatitis did not induce alterations in membrane fluidity. Lecithin increased both membrane fluidity and LDH r elease. These observations suggest that this increase in membrane flui dity of the pancreatic acini may be related to membrane alteration and to functional damage of the acini. These observation can serve as a w indow to detect the development of acute pancreatitis at an early stag e.