Document Detail


Control of Ca2+ wave propagation in mouse pancreatic acinar cells.
MedLine Citation:
PMID:  9530097     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have investigated control mechanisms involved in the propagation of agonist-induced Ca2+ waves in isolated mouse pancreatic acinar cells. Using a confocal laser-scanning microscope, we were able to show that maximal stimulation of cells with acetylcholine (ACh, 500 nM) or bombesin (1 nM) caused an initial Ca2+ release of comparable amounts with both agonists at the luminal cell pole. Subsequent Ca2+ spreading to the basolateral membrane was faster with ACh (17.3 +/- 5.4 microns/s) than with bombesin (8.0 +/- 2.2 microns/s). The speed of bombesin-induced Ca2+ waves could be increased up to the speed of ACh-induced Ca2+ waves by inhibition of protein kinase C (PKC). Activation of PKC significantly decreased the speed of ACh-induced Ca2+ waves but had only little effect on bombesin-evoked Ca2+ waves. Within 3 s after stimulation, production of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] was higher in the presence of ACh compared with bombesin, whereas bombesin induced higher levels of diacylglycerol (DAG) than ACh. These data suggest that the slower propagation speed of bombesin-induced Ca2+ waves is due to higher activation of PKC in the presence of bombesin compared with ACh. The higher increase in bombesin-compared with ACh-induced DAG production is probably due to activation of phospholipase D (PLD). Inhibition of the PLD-dependent DAG production by preincubation with 0.3% butanol led to an acceleration of the bombesin-induced Ca2+ wave. In further experiments, we could show that ruthenium red (100 microM), an inhibitor of Ca(2+)-induced Ca2+ release in skeletal muscle, also decreased the speed of ACh-induced Ca2+ waves. The effect of ruthenium red was not additive to the effect of PKC activation. From the data, we conclude that, following Ins(1,4,5)P3-induced Ca2+ release in the luminal cell pole, secondary Ca2+ release from stores, which are located in series between the luminal and the basal plasma membrane, modifies Ca2+ spreading toward the basolateral cell side by Ca(2+)-induced Ca2+ release. Activation of PKC leads to a reduction in Ca2+ release from these stores and therefore could explain the slower propagation of Ca2+ waves in the presence of bombesin compared with ACh.
Authors:
F Pfeiffer; L Sternfeld; A Schmid; I Schulz
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The American journal of physiology     Volume:  274     ISSN:  0002-9513     ISO Abbreviation:  Am. J. Physiol.     Publication Date:  1998 Mar 
Date Detail:
Created Date:  1998-04-24     Completed Date:  1998-04-24     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0370511     Medline TA:  Am J Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  C663-72     Citation Subset:  IM    
Affiliation:
Institute of Physiology II, University of the Saarland, Homburg, Germany.
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MeSH Terms
Descriptor/Qualifier:
Acetylcholine / metabolism
Animals
Bombesin / pharmacology
Calcium / metabolism*
Calcium Channels / drug effects,  metabolism
Calcium-Transporting ATPases / antagonists & inhibitors
Endoplasmic Reticulum / drug effects,  enzymology
Enzyme Activation
Enzyme Inhibitors / pharmacology
Hydroquinones / pharmacology
Indicators and Reagents / pharmacology
Inositol 1,4,5-Trisphosphate / metabolism
Male
Mice
Pancreatic Neoplasms / metabolism*
Periodicity
Phosphatidylinositol 4,5-Diphosphate / metabolism
Protein Kinase C / antagonists & inhibitors
Ruthenium Red / pharmacology
Signal Transduction
Type C Phospholipases / metabolism
Chemical
Reg. No./Substance:
0/Calcium Channels; 0/Enzyme Inhibitors; 0/Hydroquinones; 0/Indicators and Reagents; 0/Phosphatidylinositol 4,5-Diphosphate; 11103-72-3/Ruthenium Red; 1948-33-0/2-tert-butylhydroquinone; 31362-50-2/Bombesin; 51-84-3/Acetylcholine; 7440-70-2/Calcium; 85166-31-0/Inositol 1,4,5-Trisphosphate; EC 2.7.11.13/Protein Kinase C; EC 3.1.4.-/Type C Phospholipases; EC 3.6.1.8/Calcium-Transporting ATPases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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