Effect of translocator protein (18 kDa)‐ligand binding on neurotransmitter‐induced salivary secretion in rat submandibular glands

Abstract

Background information. TSPO (translocator protein), previously known as PBR (peripheral-type benzodiazepine receptor), is a ubiquitous 18 kDa transmembrane protein that participates in diverse cell functions. High-affinity TSPO ligands are best known for their ability to stimulate cholesterol transport in organs synthesizing steroids and bile salts, although they modulate other physiological functions, including cell proliferation, apoptosis and calcium-dependent transepithelial ion secretion. In present study, we investigated the localization and function of TSPO in salivary glands.Results. Immunohistochemical analysis of TSPO in rat salivary glands revealed that TSPO and its endogenous ligand, DBI (diazepam-binding inhibitor), were present in duct and mucous acinar cells. TSPO was localized to the mitochondria of these cells, whereas DBI was cytosolic. As expected, mitochondrial membrane preparations, which were enriched in TSPO, exhibited a high affinity for the TSPO drug ligand, 3 H-labelled PK 11195, as shown by B max and K d values of 10.0 + − 0.5 pmol/mg and 4.0 + − 1.0 nM respectively. Intravenous perfusion of PK 11195 increased the salivary flow rate that was induced by muscarinic and α-adrenergic agonists, whereas it had no effect when administered alone. Addition of PK 11195 also increased the K + , Na + , Cl − and protein content of saliva, indicating that this ligand modulated secretion by acini and duct cells.Conclusions. High-affinity ligand binding to mitochondrial TSPO modulates neurotransmitter-induced salivary secretion by duct and mucous acinar cells of rat submandibular glands.

Translocator protein (Tspo) gene promoter-driven green fluorescent protein synthesis in transgenic mice: an in vivo model to study Tspo transcription

“…Interestingly, the presence of Tspo -AcGFP is consistent with previous immunohistochemical analyses of TSPO in the mucous acinar cells and duct of rat submandibular glands, implying a role in modulating neurotransmitter-induced salivary secretion (Ostuni et al 2008). Notably, TSPO is also expressed in hepatocytes, which supports previous reports of the presence of TSPO in the liver, demonstrated by radioligand binding assays (Woods et al 1996) and northern blot analysis (Gazouli et al 2002).…”

Overexpression of translocator protein in inflammatory bowel disease: Potential diagnostic and treatment value

“…Paraffin sections of human or animal tissues were immunostained with rabbit anti-TSPO peptide affinity-purified polyclonal antibody (1:100)22. Dual immunofluorescence staining for TSPO and voltage-dependent anionic channel (VDAC) and subsequent analysis were performed as previously described22.…”

“…Dual immunofluorescence staining for TSPO and voltage-dependent anionic channel (VDAC) and subsequent analysis were performed as previously described22. Control experiments included the absence of the primary antibody and immunoabsorption (8 µg of recombinant 18 kDa TSPO per ml of diluted antibody22,23). …”

Genetics and genomics of alcohol responses in Drosophila

“…TSPO interacts with the diazepam binding inhibitor (DBI), which has been proposed to contribute to drug dependence. DBI can reduce GABA A receptor activity (Bormann, 1991; Ostuni et al , 2008). Mutations in the TSPO gene affect ethanol resistance in a sex-specific manner that appears to be mediated in part through ROS signaling and Caspase activity (Lin et al , 2015).…”