Characterization of beta-adrenergic receptors in DiFi and HT-29 cells.
The beta-adrenergic receptors present in two human colorectal adenocarcinoma cell lines were characterized by measuring specific binding of [125I]-cyanopindolol (CYP). Whole, cultured, DiFi (derived from a familial adenomatous polyposis [FAP] patient) and HT-29 cells were used in radioligand binding assays. Scatchard analysis of specific 125I-CYP binding gave KDS of 38.6 +/- 5.7 pM in DiFi cells and 54 +/- 9.1 pM in HT-29 cells. However, binding site density (Bmax) in the DiFi cells was greater than that in HT-29 cells. In DiFi cells, the kinetically determined KD was similar to that calculated from Scatchard analysis. Studies in DiFi cells of the displacement of specific 125I-CYP binding by nonselective (propranolol), beta 1-selective (metoprolol and atenolol), and beta 2-selective (ICI 118-551) antagonists revealed only a single class of beta 2-adrenergic receptors. This provides the first evidence that colorectal adenocarcinoma cell lines contain beta-adrenergic receptors and shows that only beta 2-adrenergic receptors are present in DiFi cells. Mechanisms possibly affecting beta-adrenergic-receptor expression in such cells are discussed in relation to colon carcinogenesis.
Department of Pharmacology, Creighton University School of Medicine, Omaha, Nebraska 68178.
P W
PW
Abel
W
W
Zeng
D M
DM
Wildrick
M C
MC
Makoid
B M
BM
Boman
D000230:Adenocarcinoma / Q000378:metabolism*; D011125:Adenomatous Polyposis Coli / Q000378:metabolism*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D001262:Atenolol / Q000494:pharmacology; D001667:Binding, Competitive; D003110:Colonic Neoplasms / Q000378:metabolism*; D006801:Humans; D020120:Iodocyanopindolol; D007700:Kinetics; D008790:Metoprolol / Q000494:pharmacology; D010869:Pindolol / Q000031:analogs & derivatives* / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C026777:ICI 118551; D001262:Atenolol; D020120:Iodocyanopindolol; D011433:Propranolol; D010869:Pindolol; D008790:Metoprolol