Radioligand binding characteristics of beta 2-adrenoceptors of cultured melanoma cells.
The existence of beta-adrenoceptors on intact cells of the human malignant melanoma cell line A-375 was investigated using the binding properties of the tritiated radioligand (-)-[3H]CGP-12177, a hydrophilic non-selective beta-adrenoceptor antagonist. Displacement experiments of the radioligand from its binding site were performed with antagonists and agonists to determine the beta-adrenoceptor subtype selectivity. The binding of (-)-[3H]CGP-12177 was saturable, of high affinity (KD = 0.025 nmol/l, n = 12) and was rapid and readily reversible. The maximal number of binding sites (Bmax) was 33.5 +/- 1.9 fmol/10(7) cells or 2018 +/- 114 receptors per cell. beta-adrenoceptor antagonists inhibited binding of the radioligand with monophasic displacement curves. IC50 values were (nmol/l): propranolol (non-selective) 2.82, alprenolol (non-selective) 2.0, ICI 118,551 (beta 2-selective) 3.5 and bisoprolol (beta 1-selective) 2200. Agonists inhibited binding in the order of potency of isoprenaline greater than adrenaline greater than noradrenaline. It is concluded that cells of the melanoma cell line A-375 contain a homogeneous population of beta 2-adrenoceptors.
Steinkraus
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V
Abteilung Allgemeine Pharmakologie, Universitäts-Krankenhaus Eppendorf, Hamburg, F.R.G.
Nose
M
M
Mensing
H
H
Körner
C
C
D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008545:Melanoma / Q000032:analysis*; D011412:Propanolamines; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000032:analysis*; D012878:Skin Neoplasms / Q000032:analysis*; D014407:Tumor Cells, Cultured / Q000032:analysis
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C057209:CGP 12177-NBD; D009327:4-Chloro-7-nitrobenzofurazan