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Activation of the Particulate and Not the Soluble Guanylate Cyclase Leads to the Inhibition of Ca2+ Extrusion through Localized Elevation of cGMP

We examined whether localized increases in cytosolic cGMP have distinct regulatory effects on the concentration of cytosolic free Ca 2+ in ECV304 cells. Stimulation of the particulate guanylate cyclase by brain-type natriuretic peptide in fura-2-loaded cells caused a profound potentiation of the ATP...

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Bibliographic Details
Published in:The Journal of biological chemistry 2000-08, Vol.275 (34), p.25892-25899
Main Authors: Zolle, O, Lawrie, A M, Simpson, A W
Format: Article
Language:English
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Summary:We examined whether localized increases in cytosolic cGMP have distinct regulatory effects on the concentration of cytosolic free Ca 2+ in ECV304 cells. Stimulation of the particulate guanylate cyclase by brain-type natriuretic peptide in fura-2-loaded cells caused a profound potentiation of the ATP-stimulated and thapsigargin-stimulated rise in cytosolic free Ca 2+ . This effect is mediated by the inhibition of Ca 2+ extrusion via the plasma membrane Ca 2+ -ATPase pump. Furthermore, the addition of brain-type natriuretic peptide caused the partial inhibition of cation influx in ATP-stimulated cells. In contrast, elevation of cytosolic cGMP by activation of the soluble guanylate cyclase induced by the addition of sodium nitroprusside causes an increased reuptake of Ca 2+ into the intracellular stores without affecting cation influx or Ca 2+ efflux. Thus, localized pools of cGMP play distinct regulatory roles in the regulation of Ca 2+ homeostasis within individual cells. We define a new role for natriuretic peptides in the inhibition of Ca 2+ efflux that leads to the potentiation of agonist-evoked increases in cytosolic free Ca 2+ .
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M000786200