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

OSTUNI MA, TUMILASCI OR, PÉRANZI G, CARDOSO EML, CONTRERAS LN, ARREGGER AL, PAPADOPOULOS V, LACAPERE JJ

BIOLOGY OF THE CELL

Año: 2008 vol. 100 p. 427 - 439

0248-4900

Background information: Translocator protein (TSPO), previously known as peripheral-type benzodiazepine receptor (PBR, 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. Here, we set out to investigate the localization and function of TSPO in salivary glands. benzodiazepine receptor (PBR), is a ubiquitous 18 kDa transmembrane protein thatparticipates 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. Results: Immunohistochemical analysis of TSPO in rat salivary glands revealed that TSPO and its endogenous ligand, diazepam binding inhibitor (DBI), were present in duct andmucous acinar cells. TSPO was localized to the mitochondria of these cells, while DBI was cytosolic. As expected, mitochondrial membrane preparations, which were enriched in TSPO, exhibited high affinity for the TSPO drug ligand, [3H]PK 11195, as shown by Bmax and Kd 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 induced by muscarinic and ��-adrenergic agonists, whereas it had no effect when administered alone. Conclusions: High affinity ligand binding to mitochondrial TSPO modulates neurotransmitter-induced salivary secretion by duct and mucous acinar cells of rat submandibular glands agonists, whereas it had no effect when administered alone.