Neurotensin high affinity binding sites and endopeptidase 24.11 are present respectively in the meningothelial and in the fibroblastic components of human meningiomas.
The presence of neurotensin receptors and endopeptidase 24.11 (E-24.11) in 16 human meningioma specimens, obtained at surgery, was assessed by measuring the binding of 125I-[tyrosyl3]neurotensin(1-13) (125I-NT) and the inhibitor 3H-N(2RS)-3-hydroxyaminocarbonyl-2-benzyl-1-oxopropyl)glycine (3H-HACBO-Gly), for the receptor and enzyme, respectively. E-24.11 activity was also measured. Autoradiography, on the 16 meningiomas, showed that specific 125I-NT labeling (nonspecific labeling was assessed in the presence of excess NT) was exclusively located in the meningothelial regions. In contrast, specific 3H-HACBO-Gly labeling (nonspecific labeling was assessed in the presence of an excess of the E-24.11 inhibitor thiorphan) was exclusively found in fibroblastic regions. No specific labeling of either ligand was found on collagen or blood vessels. In vitro binding assays were performed on membranes of 10 of the 16 meningiomas. In the 4 meningiomas rich in meningothelial cells, 125I-NT specifically bound to one population of sites with Bmax ranging from 57 to 405 fmol/mg protein and Kd around 0.3 nM. These sites share common properties with the brain NT receptor, since the carboxy terminal acetyl NT(8-13) fragment bound to the same sites but with a higher affinity. The carboxy terminal analogue of NT, neuromedin N, also bound to the same sites with a 10-fold lower affinity and the sites were bradykinin and levocabastine insensitive. In the 4 meningiomas rich in fibroblastic cells, 3H-HACBO-Gly specifically bound to one population of sites with Bmax ranging from 251 to 739 fmol/mg protein and Kd around 2.8 nM.(ABSTRACT TRUNCATED AT 250 WORDS)
Mailleux
P
P
Laboratory of Neuropathology and Neuropeptide Research, Faculty of Medicine, Brugmann Hospital, Bruxelles, Belgium.
Przedborski
S
S
Beaumont
A
A
Verslijpe
M
M
Depierreux
M
M
Levivier
M
M
Kitabgi
P
P
Roques
B P
BP
Vanderhaeghen
J J
JJ
D000328:Adult; D000368:Aged; D001345:Autoradiography; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D008577:Meningeal Neoplasms / Q000378:metabolism*; D008579:Meningioma / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D015260:Neprilysin / Q000378:metabolism*; D009496:Neurotensin / Q000378:metabolism*; D011869:Radioligand Assay; D018028:Receptors, Neurotensin; D017981:Receptors, Neurotransmitter / Q000378:metabolism*
D007457:Iodine Radioisotopes; D018028:Receptors, Neurotensin; D017981:Receptors, Neurotransmitter; D009496:Neurotensin; D015260:Neprilysin