Expression of a functional endothelin (ETA) receptor in human meningiomas.
Endothelin (ET) receptor subtypes (ETA and ETB) in human meningiomas were characterized using quantitative receptor autoradiography. A single class of high-affinity 125I-ET-1 binding sites was localized in all meningioma tissue studied (dissociation constant: 2.4 +/- 0.3 nM, maximum binding capacity: 319 +/- 66 fmol/mg (mean +/- standard error of the mean for 13 tumors)). Unlabeled ET-1 showed a strong affinity for 125I-ET-1 binding to tissue sections of the tumors with a 50% inhibiting concentration (IC50) of 2.9 +/- 0.7 x 10(-9) M, whereas ET-3 showed a much lower affinity (IC50: 8.4 +/- 2.5 x 10(-6) M). Sarafotoxin S6c, a selective agonist for the ETB receptor, could not compete for 125I-ET-1 binding to meningiomas. Endothelin-1 significantly stimulated deoxyribonucleic acid (DNA) synthesis in a dose-dependent manner in cultured human meningioma cells. In contrast, no significant stimulation of DNA synthesis occurred with an S6c concentration up to 10(-7) M. Pretreatment of the meningioma cells with pertussis toxin, a bacterial toxin that adds adenosine 5'-diphosphate-ribose to the alpha subunit of guanine nucleotide binding (G) proteins such as Gi or G(o), induced a concentration-dependent reduction in ET-stimulated DNA synthesis in meningioma cells, but did not affect the epidermal growth factor-induced DNA synthesis. These observations suggest that the ETA receptor is predominantly expressed in human meningioma tissue and that ET may act as a growth factor on the meningioma cells by interacting with the ETA receptor and by pertussis toxin-sensitive mechanisms.
Kitagawa
N
N
Department of Neurosurgery, Nagasaki University School of Medicine, Japan.
Tsutsumi
K
K
Niwa
M
M
Himeno
A
A
Yamashita
K
K
Shibata
S
S
Taniyama
K
K
Kurihara
M
M
Kawano
T
T
Yasunaga
A
A
D000293:Adolescent; D000368:Aged; D001345:Autoradiography; D001665:Binding Sites; D005260:Female; D006801:Humans; D008297:Male; D008577:Meningeal Neoplasms / Q000378:metabolism*; D008579:Meningioma / Q000378:metabolism*; D008875:Middle Aged; D017466:Receptors, Endothelin / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism; D014018:Tissue Distribution
D017466:Receptors, Endothelin; D013936:Thymidine