Kinetics of calcitonin receptor internalization in lung cancer (BEN) and osteogenic sarcoma (UMR 106-06) cells.
The fate of 125I-labeled calcitonin and calcitonin receptors in BEN and UMR 106-06 cells was studied after binding of the ligand. At 37 degrees C but not at 4 degrees C, 125I-labeled salmon calcitonin bound to both cell types and was internalized as evidenced by increasing resistance to removal by acid pH. This process was dependent on de novo protein synthesis. Cells were pretreated with salmon calcitonin and washed with acidified buffer to release cell-surface bound hormone and to allow assessment of cell-surface receptor concentration. It was found that initially there was a temperature- and time-dependent calcitonin-induced loss of binding capacity after exposure to salmon calcitonin, suggestive of endocytosis of the calcitonin-receptor complex. In the continued presence of calcitonin, receptors were lost only at the same rate as the normal turnover of calcitonin receptors as assessed in the presence of cycloheximide. These data are consistent with the presence of two functional populations of calcitonin receptors, only one of which is induced to internalize by ligand binding.
Findlay
D M
DM
Department of Clinical Pharmacology, Austin Hospital, Heidelberg, Victoria, Australia.
Martin
T J
TJ
D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism*; D002116:Calcitonin / Q000493:pharmacokinetics*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D004705:Endocytosis; D006863:Hydrogen-Ion Concentration; D008175:Lung Neoplasms / Q000378:metabolism*; D012516:Osteosarcoma / Q000378:metabolism*; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012474:Salmon; D013696:Temperature; D014407:Tumor Cells, Cultured
D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface; D002116:Calcitonin; D003513:Cycloheximide