Document Detail

Cell content of phosphatidylinositol (4,5)bisphosphate in Ehrlich mouse ascites tumour cells in response to cell volume perturbations in anisotonic and in isosmotic media.
MedLine Citation:
PMID:  17556394     Owner:  NLM     Status:  MEDLINE    
The labelling pattern of cellular phosphoinositides (PtdInsP(n)) was studied in Ehrlich ascites cells labelled in vivo for 24 h with myo-[2-(3)H]- or l-myo-[1-(3)H]inositol and exposed to anisotonic or isosmotic volume perturbations. In parallel experiments the cell volume ([(14)C]3-OMG space) was monitored. In hypotonic media the cells initially swelled osmotically and subsequently as expected showed a regulatory volume decrease (RVD) response. Concurrently, the cell content of PtdInsP(2) showed a marked, transient decrease and the content of PtdInsP a small, transient increase. The changes in PtdInsP(2) and PtdInsP content increased progressively with the extent of hypotonicity (in the range 1.00-0.50 relative osmolarity). No evidence was found for either hydrolysis of PtdInsP(2) or formation of PtdInsP(3). In hypertonic medium (relative osmolarity 1.50), cells initially shrank osmotically and subsequently as expected showed a small regulatory volume increase (RVI) response. Concurrently, the cell content of PtdInsP(2) showed a marked increase and the content of PtdInsP a small decrease, i.e. changes in the opposite direction of those seen in hypotonic media. In isosmotic media with high (100 mm) or low (0.8 mm) K(+) concentration, cells slowly swelled or shrank due to uptake or loss of isosmotic KCl. Under these conditions, with largely unchanged intracellular ionic strength, the cell content of PtdInsP(2) and PtdInsP remained constant. Our results show that PtdInsP(2) is not volume sensitive per se, and moreover that the regulatory volume adjustments in Ehrlich ascites cells are not mediated by PtdInsP(2) hydrolysis and its subsequent production of second messengers. The simplest interpretation of the observed effects would be that PtdInsP(2) is controlled by ionic strength, probably via activation/inhibition of phosphoinositide-specific phosphatases/kinases. In Ehrlich ascites cells, as shown previously, the opposing ion channels and transporters activated during RVD and RVI, respectively, are controlled with tight negative coordination by a common cell volume 'set-point' that is shifted in anisotonic media, but unchanged during cell swelling in isosmotic high K(+) medium. We hypothesize that PtdInsP(2) might orchestrate this 'set-point' shift.
Doris K Nielsen; Annelie Kolbjørn Jensen; Henrik Harbak; Søren C Christensen; Lars Ole Simonsen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-06-07
Journal Detail:
Title:  The Journal of physiology     Volume:  582     ISSN:  0022-3751     ISO Abbreviation:  J. Physiol. (Lond.)     Publication Date:  2007 Aug 
Date Detail:
Created Date:  2007-08-03     Completed Date:  2007-09-26     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  0266262     Medline TA:  J Physiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1027-36     Citation Subset:  IM    
August Krogh Institute, University of Copenhagen, Universitetsparken 13, DK-2100 Copenhagen Ø, Denmark.
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MeSH Terms
Body Water / physiology
Carcinoma, Ehrlich Tumor / pathology,  physiopathology*
Cell Size
Culture Media
Inositol Phosphates / physiology
Mice, Inbred Strains
Phosphatidylinositol 4,5-Diphosphate / metabolism*
Reg. No./Substance:
0/Culture Media; 0/Inositol Phosphates; 0/Phosphatidylinositol 4,5-Diphosphate

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