Evidence that up-regulation of the parotid Na(+)-K(+)-2Cl- cotransporter by hypertonic shrinkage is not duplicated by isotonic shrinkage.
The application of Ca2+ mobilizing secretagogues to rat parotid acini results in a significant decrease in cell volume (15-30%) due to isotonic salt loss. It is often assumed that the effects of such an isotonic volume decrease can be mimicked by anisotonic cell shrinkage. We demonstrate that the Na(+)-K(+)-2Cl- cotransporter in these cells is up-regulated by Ca2+ mobilizing secretagogues as well as by cell shrinkage in hypertonic media. However, we find that although the protein kinase inhibitors staurosporine (0.3 microM) and K252a (0.6 microM) significantly blunt the latter up-regulation, they are without effect on the former. These observations suggest that hypertonic and isotonic shrinkage do not result in the activation of the same intracellular signalling pathways, and indicate that anisotonic volume perturbations may not provide good experimental models of physiologic isotonic volume changes.
Ferri
C
C
Clinical Investigations and Patient Care Branch, National Institute of Dental Research, National Institutes of Health, Bethesda MD 20892, USA.
Evans
R L
RL
Paulais
M
M
Tanimura
A
A
Turner
R J
RJ
D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D048429:Cell Size; D002712:Chlorides / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D018721:Muscarinic Agonists / Q000494:pharmacology; D010306:Parotid Gland / Q000166:cytology* / Q000187:drug effects*; D011188:Potassium / Q000378:metabolism*; D047428:Protein Kinase Inhibitors; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism*; D028021:Sodium-Potassium-Chloride Symporters; D019311:Staurosporine / Q000494:pharmacology; D015854:Up-Regulation
D002352:Carrier Proteins; D002712:Chlorides; D008565:Membrane Proteins; D018721:Muscarinic Agonists; D047428:Protein Kinase Inhibitors; D028021:Sodium-Potassium-Chloride Symporters; D000643:Ammonium Chloride; D002217:Carbachol; D012964:Sodium; D019311:Staurosporine; D011188:Potassium; D002118:Calcium