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Dual effect of H2O2 on the Regulation of Cholecystokinin-induced Amylase Release in Rat Pancreatic Acinar Cells

서정택|이진학|안정미
대한구강생물학회 (Korean Academy Of Oral Biology)|2006.12|International Journal of Oral Biology|제31권 제4호|pp. 127-133

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주제분류치의학

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Abstract

H2O2, a member of reactive oxygen species (ROS), is known to be involved in the mediation of physiological functions in a variety of cell types. However, little has been known about the physiological role of H2O2 in exocrine cells. Therefore, in the present study, the effect of H2O2 on cholecystokinin (CCK)-evoked Ca2+ mobilization and amy-lase release was investigated in rat pancreatic acinar cells. Stimulation of the acinar cells with sulfated octapeptide form of CCK (CCK-8S) induced biphasic increase in amylase release. Addition of 30 M H2O2 enhanced amylase release caused by 10 pM CCK-8S, but inhibited the amylase release induced by CCK-8S at concentrations higher than 100 pM. An ROS scavenger, 10 M Mn(III)tetrakis(4-benzoic acid)porphyrin chloride, increased amylase release caused by CCK-8S at concentrations higher than 100 pM, although lower concentrations of CCK-8S-induced amylase release was not affected. To examine whether the effect of H2O2 on CCK-8S-induced amylase release was exerted via modu-lation of intracellular Ca2+ signaling, we measured the changes in intracellular Ca2+ concentration ([Ca2+]i) in fura-2 loaded acinar cells. Although 30 M H2O2 did not induce any increase in [Ca2+]i by itself, it increased the frequency and amplitude of [Ca2+]i oscillations caused by 10 pM CCK-8S. However, 30 M H2O2 had little effect on 1 nM CCK-8S-induced increase in [Ca2+]i. ROS scavenger, 1 mM N-acetylcysteine, did not affect [Ca2+]i changes induced by 10 pM or 1 nM CCK-8S. Therefore, it was concluded that 30 M H2O2 enhanced low concentration of CCK-8S-induced amylase release probably by increasing [Ca2+]i oscillations while it inhibited high concentration of CCK-8S-induced amylase release.

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