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Caloxin: a novel plasma membrane Ca2+ pump inhibitor.
J Chaudhary1, M Walia, J Matharu
1Department of Medicine, McMaster University, 1200 Main St., Hamilton, Ontario, Canada L8N 3Z5.
American Journal of Physiology. Cell Physiology
|March 14, 2001
Summary
Researchers identified caloxin 2A1, a novel peptide inhibitor targeting the plasma membrane calcium pump (PM Ca2+ pump). This discovery offers a new tool for studying cellular calcium regulation and its physiological effects.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- The plasma membrane calcium pump (PM Ca2+ pump) is crucial for maintaining low intracellular calcium levels.
- Extracellular inhibitors for the PM Ca2+ pump are currently unknown, unlike those for the Na+ pump.
Purpose of the Study:
- To define and characterize extracellular inhibitors of the PM Ca2+ pump, termed caloxins.
- To investigate the properties and effects of a novel caloxin, caloxin 2A1.
Main Methods:
- Screening a random peptide phage display library to identify peptides binding to the PM Ca2+ pump.
- Assessing caloxin 2A1's inhibitory activity on Ca2+-Mg2+-ATPase in human erythrocyte leaky ghosts.
- Evaluating caloxin 2A1's effects on other ATPases and its impact on vascular endothelium.
Main Results:
- Caloxin 2A1 specifically inhibits Ca2+-Mg2+-ATPase in erythrocyte ghosts without affecting other ATPases.
- It also inhibits a partial reaction of the PM Ca2+ pump, the formation of a 140-kDa acylphosphate.
- Caloxin 2A1 induces endothelium-dependent relaxation in vascular tissue.
Conclusions:
- Caloxin 2A1 is a novel, extracellularly acting inhibitor of the PM Ca2+ pump.
- This peptide provides a new pharmacological tool for studying calcium homeostasis and related physiological processes.