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-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+).
Zolle
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Department of Human Anatomy and Cell Biology, University of Liverpool, New Medical School, Ashton St., Liverpool L69 3GE, United Kingdom.
Lawrie
A M
AM
Simpson
A W
AW
D000255:Adenosine Triphosphate / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002460:Cell Line; D006152:Cyclic GMP / Q000378:metabolism*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D004789:Enzyme Activation; D016257:Fura-2; D006162:Guanylate Cyclase / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D020097:Natriuretic Peptide, Brain / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D012995:Solubility; D019284:Thapsigargin / Q000494:pharmacology
D020097:Natriuretic Peptide, Brain; D009599:Nitroprusside; D003995:Dibutyryl Cyclic GMP; D019284:Thapsigargin; D000255:Adenosine Triphosphate; D006162:Guanylate Cyclase; D000252:Calcium-Transporting ATPases; D006152:Cyclic GMP; D002118:Calcium; D016257:Fura-2