Changes in cytosolic Ca²⁺ concentration are critical for numerous hepatocyte functions. While it is well-known that InsP₃ receptors (InsP₃-Rs) play a crucial role in this process, the regulation of the three types of InsP₃ receptors by other proteins remains largely unknown. It has been shown in neuroblastoma cells that sigma-1 receptor (s1-R) could interact with InsP₃ receptors and affect Ca²⁺ signaling. The sigma-1 receptors, initially described as a subtype of opiate receptors, is highly expressed in the central nervous system and in the liver. We thus examined whether sigma-1 receptors could be involved in the regulation of Ca²⁺ signaling in hepatocytes.

Subcellular fractionation of liver membranes shown that s1-R and InsP₃T1-R were distributed in all fractions analyzed. In contrast InsP₃T2-R was found in a particular fraction enriched with markers of baso-lateral membranes. Immunofluorescence experiments confirm these observations. InsP₃T2-R was concentrated near the canalicular pole in hepatocytes, whereas InsP₃T1-R and s1-R were found to be homogeneously distributed within the cytosol. Specific s1-R ligands inhibited noradrenaline induced Ca²⁺ increase but did not modify InsP₃ induced Ca²⁺ release in permeabilized hepatocytes. Moreover, intracellular Ca²⁺ signals were not affected by the overexpression of s1-R in HepG2 cells. Our results suggest that s1-R is not involved in the regulation of InsP₃ induced Ca²⁺ signals in hepatocytes.