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Cell density modulates the decrease of cytosolic free Ca2+ induced by atrial natriuretic hormone,
F Lermioglu1, J Goyal, A Hassid
1Department of Pharmacology, New York Medical College, Valhalla 10595.
Insights
Cell density enhances the effect of cyclic GMP (cGMP)-elevating agents on intracellular calcium in mesangial cells. This modulation is independent of cell proliferation, highlighting cell density
Area of Science:
- Cellular Physiology
- Renal Cell Biology
- Signal Transduction
Background:
- Cyclic GMP (cGMP)-elevating agents like atrial natriuretic peptide (ANP) and NO-generating vasodilators reduce cytosolic free Ca2+ in mesangial cells.
- The influence of cellular environment, specifically cell density, on this Ca2+ regulation is not fully understood.
Purpose of the Study:
- To investigate the role of cell density in modulating the decrease in cytosolic free Ca2+ induced by cGMP-elevating vasodilators.
- To determine if the cells' proliferative status affects this modulation.
Main Methods:
- Cultured rat mesangial cells were used at varying densities.
- Measurements of cytosolic free Ca2+ levels were performed.
- cGMP accumulation was quantified following stimulation with atrial natriuretic peptide (99-126) [ANP (99-126)] and S-nitroso-N-acetylpenicillamine (SNAP).
Main Results:
- Increased cell density significantly correlated with a greater decrease in cytosolic free Ca2+ induced by ANP (99-126) and SNAP.
- This effect was independent of the cells' proliferative status.
- Higher cell density led to greater fold stimulation of cGMP accumulation, with 8-bromo cGMP being more effective in high-density cells.
Conclusions:
- Cell density, not proliferative status, is a key modulator of intracellular Ca2+ dynamics in rat mesangial cells.
- The enhanced effectiveness of ANP (99-126) and SNAP in high-density cells is partly due to increased effectiveness of endogenous cGMP.
- These findings are relevant for understanding the regulation of mesangial cell function by vasodilators and cGMP.
Abstract:
Cyclic GMP-elevating agents, including atrial natriuretic hormone and NO-generating vasodilators, decrease cytosolic free Ca2+ levels in mesangial cells. We have investigated the role of cell density as a modulator of the decrease in cytosolic free Ca2+ induced by the cyclic GMP (cGMP)-elevating vasodilators atrial natriuretic peptide (99-126) [ANP (99-126); 'atriopeptin 28'] and the NO-generating vasodilator S-nitroso-N-acetylpenicillamine (SNAP), in cultured rat mesangial cells. Increasing cell density was significantly correlated with the decrease in cytosolic free Ca2+ induced by ANP (99-126) or SNAP. Moreover, this effect was independent of the cells' proliferative status. ANP (99-126) and SNAP induced greater fold stimulation of cGMP accumulation in high-density cells, but the levels of cGMP elicited by high concentrations of ANP (99-126) or SNAP were similar in high- and low-density cells. 8-Bromo cGMP was more effective in decreasing cytosolic free Ca2+ in high- than in low-density cells, suggesting that the greater effectiveness of ANP (99-126) and SNAP was, in part, due to greater effectiveness of endogenous cGMP in high-density cells. The results document that cell density, but not proliferative status, plays an important role in the modulation of intracellular Ca2+ dynamics in rat mesangial cells by atriopeptins, NO-generating vasodilators and cGMP.