Distribution, pharmacological characterization and function of the 18 kDa translocator protein in rat small intestine.
BACKGROUND
The TSPO (18 kDa translocator protein) is a mitochondrial transmembrane protein involved in cholesterol transport in organs that synthesize steroids and bile salts. Different natural and synthetic high-affinity TSPO ligands have been characterized through their ability to stimulate cholesterol transport, but also to stimulate other physiological functions including cell proliferation, apoptosis and calcium-dependent transepithelial ion secretion. Here, we investigate the localization and functions of TSPO in the small intestine.


RESULTS
TSPO was present in enterocyte mitochondria but not in rat intestinal goblet cells. Enterocyte cytoplasm also contained the endogenous TSPO ligand, polypeptide DBI (diazepam-binding inhibitor). Whereas intestinal TSPO had high affinity for the synthetic ligand PK 11195, the pharmacological profile of TSPO in the duodenum was distinct from the jejunum and ileum. Specifically, benzodiazepine Ro5-4864 and protoporphyrin IX showed 5-13-fold lower affinity for duodenal TSPO. The mRNA and protein ratios of TSPO to other mitochondrial membrane proteins VDAC (voltage-dependent anion channel) and ANT (adenine nucleotide transporter) were significantly different. PK 11195 stimulated calcium-dependent chloride secretion in the duodenum and calcium-dependent chloride absorption in the ileum, but did not affect jejunum ion transport.


CONCLUSIONS
The functional differences in subpopulations of TSPO in different regions of the intestine could be related to structural organization of mitochondrial protein complexes that mediate the ability of TSPO to modulate either chloride secretion or absorption in the duodenum and ileum respectively.
Ostuni
Mariano Anibal
MA
Unité INSERM U773, Centre de Recherche Biomédicale Bichat Beaujon CRB3, Université Paris 7 Denis Diderot, BP 416, F-75018 Paris, France.
Péranzi
Gabriel
G
Ducroc
Robert A
RA
Fasseu
Magali
M
Vidic
Branislav
B
Dumont
Janice
J
Papadopoulos
Vassilios
V
Lacapere
Jean-Jacques
JJ
D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D026261:Diazepam Binding Inhibitor / Q000737:chemistry / Q000378:metabolism; D004386:Duodenum / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D020895:Enterocytes / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D058787:GABA-A Receptor Antagonists; D007082:Ileum / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D020128:Inhibitory Concentration 50; D007413:Intestinal Mucosa / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D007421:Intestine, Small / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D017136:Ion Transport / Q000502:physiology; D007546:Isoquinolines / Q000378:metabolism / Q000494:pharmacology; D007583:Jejunum / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D008024:Ligands; D008297:Male; D008566:Membranes / Q000378:metabolism; D008928:Mitochondria / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D033681:Mitochondrial Membrane Transport Proteins / Q000037:antagonists & inhibitors; D000083162:Mitochondrial Permeability Transition Pore; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009206:Myocardium; D009928:Organ Specificity; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar / Q000378:metabolism; D011963:Receptors, GABA-A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013363:Submandibular Gland / Q000378:metabolism
D002352:Carrier Proteins; D026261:Diazepam Binding Inhibitor; D058787:GABA-A Receptor Antagonists; D007546:Isoquinolines; D008024:Ligands; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D024101:Mitochondrial Proteins; D011963:Receptors, GABA-A; C069997:Tspo protein, rat; C037850:PK 11195