Cell density modulates the decrease of cytosolic free Ca2+ induced by atrial natriuretic hormone, S-nitroso-N-acetylpenicillamine and 8-bromo cyclic GMP in cultured rat mesangial cells.
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.
Lermioglu
F
F
Department of Pharmacology, New York Medical College, Valhalla 10595.
Goyal
J
J
Hassid
A
A
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002452:Cell Count; D002455:Cell Division; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004232:Diuretics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D026423:S-Nitroso-N-Acetylpenicillamine; D014665:Vasodilator Agents / Q000494:pharmacology*
D004232:Diuretics; D010446:Peptide Fragments; D014665:Vasodilator Agents; C016276:8-bromocyclic GMP; D026423:S-Nitroso-N-Acetylpenicillamine; D009320:Atrial Natriuretic Factor; D010396:Penicillamine; D006152:Cyclic GMP; D002118:Calcium