Endothelin receptor in microvessels isolated from human meningiomas: quantification with radioluminography.
1. We characterized specific 125I-endothelin-1 (125I-ET-1) binding sites in microvessels isolated from human meningiomas, using an in vitro quantitative receptor autoradiographic technique coupled to a radioluminographic imaging plate system. 2. This newly developed and highly sensitive method revealed high-affinity ET receptors present in pellet sections of the microvessels from all the meningiomas studied, regardless of histological subtypes (dissociation constant, 1.2 +/- 0.3 nM; maximum binding capacity, 185 +/- 56 fmol/mg; means +/- SE for nine tumors). 3. In five cases of meningiomas, ET-3 competed for 125I-ET-1 binding to microvessels from those tumors with a low affinity [50% inhibiting concentration (IC50) of 1.6 +/- 0.4 x 10(-6) M], and a selective ETB receptor agonist, sarafotoxin S6c, up to 10(-6) M, did not displace ET binding from the sections. 4. In the sections of microvessels from four other tumors, biphasic competition curves were obtained in the case of incubation in the presence of increasing concentrations of ET-3, with an IC50 of 1.1 +/- 0.2 x 10(-9) M for the high-affinity component and 1.6 +/- 0.3 x 10(-6) M for the low-affinity component, respectively. In addition, S6c competed for ET binding to those sections (IC50 = 2.3 +/- 0.2 x 10(-10) M) and 10(-6) M S6c displaced 30% of the control, corresponding to the high-affinity component of competition curves obtained in the presence of ET-3. 5. Our results suggest that (a) capillaries in human meningiomas express a large number of high-affinity ETA (non-ETB) receptors with a small proportion of ETB receptors, and (b) ET may have a role in neovascularization, tumor blood flow, and/or function of the blood-tumor barrier in meningioma tissues by interacting with specific receptors present on the surface of the endothelium.
Yamaga
S
S
Department of Neurosurgery, Nagasaki University School of Medicine, Japan.
Tsutsumi
K
K
Niwa
M
M
Kitagawa
N
N
Anda
T
T
Himeno
A
A
Khalid
H
H
Taniyama
K
K
Shibata
S
S
D000293:Adolescent; D000368:Aged; D001345:Autoradiography / Q000379:methods; D016232:Endothelins / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D007700:Kinetics; D008297:Male; D008577:Meningeal Neoplasms / Q000098:blood supply* / Q000601:surgery; D008579:Meningioma / Q000098:blood supply* / Q000601:surgery; D008833:Microcirculation / Q000378:metabolism*; D008875:Middle Aged; D011869:Radioligand Assay; D017466:Receptors, Endothelin / Q000032:analysis* / Q000378:metabolism
D016232:Endothelins; D007457:Iodine Radioisotopes; D017466:Receptors, Endothelin