Betaine and inositol reduce mdck cell glycerophosphocholine by stimulating its degradation. Kwon, Eugene D., Krzysztof Zablocki, Eugenia M. Peters, Kyu Yong Jung, Arlyn Garc[acute]ia-P[acute]erez, and Maurice B. Burg. Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute
APStracts 2:0258C, 1995.
The amount of glycerophosphocholine (GPC) in renal medullary cells, in vivo, and in cultured renal cells (MDCK), varies with extracellular NaCl and urea. We previously showed that this is largely due to modulation of GPC degradation, catalyzed by GPC:choline phosphodiesterase (GPC:PDE). GPC also varies inversely with the levels of other compatible osmolytes whose accumulation is induced by high tonicity. In the present study, we tested whether GPC:PDE activity and GPC degradation are affected by accumulation of other compatible osmolytes besides GPC. We find that MDCK cell GPC content decreases when the cells take up betaine and/or inositol from the medium. The effect is considerably greater for cells in isosmotic or high NaCl medium than in high urea medium. This difference is associated with suppression of betaine and inositol accumulation with high urea. We then measured GPC:PDE activity with a novel chemiluminescent assay. Addition of inositol and/or betaine to the medium greatly increases GPC:PDE activity in cells in isosmotic or high NaCl media, but to a much lesser extent in high urea medium. The increases in GPC:PDE activity, associated with the presence of betaine, are accompanied by commensurate increases in absolute rates of endogenous GPC degradation by cells in isosmotic or high NaCl medium. We found previously that in MDCK cells incubated for two days in high NaCl medium the rate of GPC synthesis from phosphatidylcholine is increased, correlated with an increase in phospholipase activity. However, in the present experiments betaine accumulation has no effect on phospholipase activity under those conditions and, thus, presumably does not affect GPC synthesis. Collectively, these data support the conclusion that betaine and/or inositol reduce GPC by increasing GPC degradation, catalyzed by GPC:PDE. This mechanism enables GPC to be reciprocally regulated relative to other compatible osmolytes, thus maintaining an appropriate total osmolyte content. 

Received 4 April 1995; accepted in final form 6 July 1995.
APS Manuscript Number C195-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 18 July 1995.