Comparison of Isotonic Activation of Cell Volume Regulation in Rat Peritoneal Mesothelial Cells and in Kidney Outer Medullary Collecting Duct Principal Cells.

Galina S Baturina,Sotirios G Zarogiannis,Claus Peter Schmitt,Liubov E Katkova,Evgeniy I Solenov

doi:10.3390/biom11101452

Abstract

In disease states, mesothelial cells are exposed to variable osmotic conditions, with high osmotic stress exerted by peritoneal dialysis (PD) fluids. They contain unphysiologically high concentrations of glucose and result in major peritoneal membrane transformation and PD function loss. The effects of isotonic entry of urea and myo-inositol in hypertonic (380 mOsm/kg) medium on the cell volume of primary cultures of rat peritoneal mesothelial cells and rat kidney outer medullary collecting duct (OMCD) principal cells were studied. In hypertonic medium, rat peritoneal mesothelial cells activated a different mechanism of cell volume regulation in the presence of isotonic urea (100 mM) in comparison to rat kidney OMCD principal cells. In kidney OMCD cells inflow of urea into the shrunken cell results in restoration of cell volume. In the shrunken peritoneal mesothelial cells, isotonic urea inflow caused a small volume increase and activated regulatory volume decrease (RVD). Isotonic myo-inositol activated RVD in hypertonic medium in both cell types. Isotonic application of both osmolytes caused a sharp increase of intracellular calcium both in peritoneal mesothelial cells and in kidney OMCD principal cells. In conclusion, peritoneal mesothelial cells exhibit RVD mechanisms when challenged with myo-inositol and urea under hyperosmolar isotonic switch from mannitol through involvement of calcium-dependent control. Myo-inositol effects were identical with the ones in OMCD principal cells whereas urea effects in OMCD principal cells led to no RVD induction.

Highlights

We demonstrate that parietal peritoneal mesothelial cells have urea and myoinositol permeability, but at lower rates than principal outer medullary collecting duct (OMCD) cells
We provide essential information of key response mechanisms of peritoneal mesothelial cells to hyperosmolality compared to OMCD cells, as present for example in patients with ascites
We provide the first evidence that peritoneal mesothelial cells under isotonic switching in hyperosmolar conditions exhibit significant regulatory volume decrease (RVD) reactions in response both in the case of myo-inositol and urea

Summary

Introduction

The maintenance of a constant cell volume in the face of extracellular and intracellular osmotic perturbations is an issue faced mainly by epithelial cells. Most cells respond to osmotic challenges by activating specific membrane transport processes that serve to return cell volume to its normal, initial value [1,2]. These processes are essential for normal cell function and survival. The key process of RVI and RVD is the gain or loss of intracellular osmotically active molecules (osmolytes) followed by an influx or efflux of extracellular water, Biomolecules 2021, 11, 1452.

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