Sigma-1 Receptor Agonist Amitriptyline Inhibits Store-Dependent Ca²⁺ Entry in Macrophages

Area of Science:

• Immunology
• Cell Biology
• Pharmacology

Background:

• Store-dependent calcium (Ca2+) entry is crucial for macrophage function.
• Endoplasmic Ca2+-ATPase inhibitors like thapsigargin and cyclopiazonic acid disrupt Ca2+ stores.
• The role of sigma-1 receptors in regulating Ca2+ entry in macrophages remains unclear.

Purpose of the Study:

• To investigate the effect of the sigma-1 receptor agonist amitriptyline on store-dependent Ca2+ entry in rat peritoneal macrophages.

Main Methods:

• Fura-2AM microfluorimetry was used to measure intracellular Ca2+ levels.
• Rat peritoneal macrophages were treated with thapsigargin or cyclopiazonic acid.
• The impact of amitriptyline on Ca2+ entry was assessed.

Main Results:

• Amitriptyline significantly inhibited thapsigargin- and cyclopiazonic acid-induced Ca2+ entry.
• This inhibition was observed for the first time in rat peritoneal macrophages.

Conclusions:

• Sigma-1 receptors, activated by amitriptyline, can inhibit store-dependent Ca2+ entry in macrophages.
• These findings suggest a novel regulatory mechanism for Ca2+ homeostasis in macrophages involving sigma-1 receptors.