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Am J Physiol Gastrointest Liver Physiol 255: G33-G39, 1988;
0193-1857/88 $5.00
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AJP - Gastrointestinal and Liver Physiology, Vol 255, Issue 1 33-G39, Copyright © 1988 by American Physiological Society


ARTICLES

Caerulein causes translocation of protein kinase C in rat acini without increasing cytosolic free Ca2+

R. Bruzzone, R. Regazzi and C. B. Wollheim
Institut de Biochimie Clinique, University of Geneva, Switzerland.

We investigated the relationships between changes in cytosolic free Ca2+ ([Ca2+]i) and amylase secretion in dispersed rat pancreatic acini. Although 10 pM caerulein did not raise [Ca2+]i, higher concentrations (1 nM) of the peptide elicited a prompt, marked, but transient (2-3 min) elevation of [Ca2+]i. Both concentrations of caerulein caused an almost identical release of amylase over a 30-min period. To investigate the mechanism(s) underlying Ca2+-independent secretion, we measured the effect of the secretagogue on protein kinase C activity and found that both caerulein concentrations caused a significant translocation of protein kinase C from the cytosolic to the microsomal fraction. Because 1 nM caerulein induced a greater enzyme secretion than 10 pM caerulein during the first 2-5 min of stimulation, we explored further the role of [Ca2+]i transients during the first minutes of secretion. Addition of ionomycin in the presence of 10 pM caerulein resulted in a rise in [Ca2+]i and enhanced secretion as a result of caerulein in a near additive fashion during the first 2 min of stimulation. Second, we pretreated acini for 5 min with 1 microM 12-O-tetradecanoylphorbol-13-acetate. This maneuver inhibited both caerulein-induced inositol trisphosphate formation and [Ca2+]i elevation. These findings were paralleled by a similar inhibition of caerulein-stimulated amylase release only during the first 5 min of secretion. These results indicate that 1) caerulein can stimulate amylase secretion independently of a concomitant [Ca2+]i rise, possibly by activation of protein kinase C, and 2) an elevation of [Ca2+]i serves as a trigger to enhance amylase release only during the initial phase of secretion.


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Am. J. Physiol. Gastrointest. Liver Physiol.Home page
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Involvement of RhoA and its interaction with protein kinase C and Src in CCK-stimulated pancreatic acini
Am J Physiol Gastrointest Liver Physiol, April 1, 1999; 276(4): G915 - G923.
[Abstract] [Full Text] [PDF]




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