Effect of translocator protein (18 kDa)-ligand binding on neurotransmitter-induced salivary secretion in rat submandibular glands.
BACKGROUND
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 alpha-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.
Ostuni
Mariano A
MA
INSERM, U773, Centre de Recherche Biomédicale Bichat Beaujon CRB3, Université Paris VII Denis Diderot, Paris, France.
Tumilasci
Omar R
OR
Péranzi
Gabriel
G
Cardoso
Estela M L
EM
Contreras
Liliana N
LN
Arregger
Alejandro L
AL
Papadopoulos
Vassilios
V
Lacapere
Jean-Jacques
JJ
D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000032:analysis / Q000378:metabolism*; D026261:Diazepam Binding Inhibitor / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D051336:Mitochondrial Membranes / Q000378:metabolism; D009092:Mucous Membrane / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000032:analysis / Q000378:metabolism*; D018987:Salivary Ducts / Q000378:metabolism / Q000648:ultrastructure; D012472:Salivation / Q000187:drug effects; D013363:Submandibular Gland / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure
D002352:Carrier Proteins; D026261:Diazepam Binding Inhibitor; D007546:Isoquinolines; D018377:Neurotransmitter Agents; D011963:Receptors, GABA-A; C069997:Tspo protein, rat; C037850:PK 11195