Caloxin: a novel plasma membrane Ca2+ pump inhibitor.
Plasma membrane (PM) Ca2+ pump is a Ca+-Mg2+-ATPase that expels Ca2+ from cells to help them maintain low concentrations of cytosolic Ca2+ . There are no known extracellularly acting PM Ca2+ pump inhibitors, as digoxin and ouabain are for Na+ pump. In analogy with digoxin, we define caloxins as extracellular PM Ca2+ pump inhibitors and describe caloxin 2A1. Caloxin 2A1 is a peptide obtained by screening a random peptide phage display library for binding to the second extracellular domain (residues 401-413) sequence of PM Ca2+ pump isoform 1b. Caloxin 2A1 inhibits Ca2+-Mg2+-ATPase in human erythrocyte leaky ghosts, but it does not affect basal Mg2+-ATPase or Na+-K+-ATPase in the ghosts or Ca2+-Mg2+-ATPase in the skeletal muscle sarcoplasmic reticulum. Caloxin 2A1 also inhibits Ca2+-dependent formation of the 140-kDa acid-stable acylphosphate, which is a partial reaction of this enzyme. Consistent with inhibition of the PM Ca2+ pump in vascular endothelium, caloxin 2A1 produces an endothelium-dependent relaxation that is reversed by N(G)-nitro-L-arginine methyl ester. Thus caloxin 2A1 is a novel PM Ca2+ pump inhibitor selected for binding to an extracellular domain.
Department of Medicine, McMaster University, 1200 Main St., Hamilton, Ontario, Canada L8N 3Z5.
J
J
Chaudhary
M
M
Walia
J
J
Matharu
E
E
Escher
A K
AK
Grover
D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D004730:Endothelium, Vascular / Q000201:enzymology; D004910:Erythrocyte Membrane / Q000201:enzymology*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D019151:Peptide Library; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D019151:Peptide Library; D010455:Peptides; C423122:caloxin 2A1; D000255:Adenosine Triphosphate; D000252:Calcium-Transporting ATPases; D002118:Calcium