Activation of the particulate and not the soluble guanylate cyclase leads to the inhibition of Ca2+ extrusion through localized elevation of cGMP

Abstract

We examined whether localized increases in cytosolic cGMP have distinct regulatory effects on the concentration of cytosolic free Ca2+ 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 Ca2+. This effect is mediated by the inhibition of Ca2+ extrusion via the plasma membrane Ca2+-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 Ca2+ into the intracellular stores without affecting cation influx or Ca2+ efflux. Thus, localized pools of cGMP play distinct regulatory roles in the regulation of Ca2+ homeostasis within individual cells. We define a new role for natriuretic peptides in the inhibition of Ca2+ efflux that leads to the potentiation of agonist-evoked increases in cytosolic free Ca2+.