Caloxin: a novel plasma membrane Ca2+ pump inhibitor

• Published in: American Journal of Physiology: Cell Physiology 2001-04, Vol.280 (4), p.C1027-C1030
• Main Authors: Chaudhary, Jyoti, Walia, Mandeep, Matharu, Jaswinder, Escher, Emanuel, Grover, Ashok K
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - metabolism; Amino Acid Sequence; Calcium - metabolism; Calcium-Transporting ATPases - antagonists & inhibitors; Endothelium, Vascular - enzymology; Erythrocyte Membrane - enzymology; Homeostasis - physiology; Humans; Membrane Proteins - genetics; Membrane Proteins - metabolism; Molecular Sequence Data; Peptide Library; Peptides - genetics; Peptides - metabolism; Signal Transduction - physiology
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.2001.280.4.c1027

1  Departments of Medicine and Biology, McMaster University, Hamilton, Ontario, Canada L8N 3Z5; and 2  Department of Pharmacology, Sherbrooke University, Sherbrooke, Quebec, Canada J1H 5N4 Plasma membrane (PM) Ca 2+ pump is a Ca 2+ -Mg 2+ -ATPase that expels Ca 2+ from cells to help them maintain low concentrations of cytosolic Ca 2+ . There are no known extracellularly acting PM Ca 2+ pump inhibitors, as digoxin and ouabain are for Na + pump. In analogy with digoxin, we define caloxins as extracellular PM Ca 2+ 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 Ca 2+ pump isoform 1b. Caloxin 2A1 inhibits Ca 2+ -Mg 2+ -ATPase in human erythrocyte leaky ghosts, but it does not affect basal Mg 2+ -ATPase or Na + -K + -ATPase in the ghosts or Ca 2+ -Mg 2+ -ATPase in the skeletal muscle sarcoplasmic reticulum. Caloxin 2A1 also inhibits Ca 2+ -dependent formation of the 140-kDa acid-stable acylphosphate, which is a partial reaction of this enzyme. Consistent with inhibition of the PM Ca 2+ 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 Ca 2+ pump inhibitor selected for binding to an extracellular domain. adenosine 5'-triphosphatase; plasma membrane calcium ATPase; transport; calcium; endothelium; erythrocytes; homeostasis; signal transduction