Internalization-sequestration and degradation of cholecystokinin (CCK) in tumoral rat pancreatic AR 4-2 J cells

Autor: Marie-Hélène Dupuche, Jean Christophe, Monique Lambert, Diem Ngoc Bui, Michal Svoboda
Rok vydání: 1990
Předmět:
Succinimides -- metabolism
Cell Membrane -- metabolism
Arsenicals
Iodine Radioisotopes
Internalization-sequestration
chemistry.chemical_compound
Tumor Cells
Cultured

Dinitrophenols -- pharmacology
Sincalide -- analogs & derivatives -- metabolism
Receptor
Internalization
media_common
Cholecystokinin
Gastrins -- metabolism
Temperature
Chloroquine
Chloroquine -- pharmacology
Sciences bio-médicales et agricoles
Hydrogen-Ion Concentration
Endocytosis
Biochemistry
Intracellular
Cytochalasin D
Pancreas -- metabolism
media_common.quotation_subject
Succinimides
Cytochalasin D -- pharmacology
Endocytosis -- drug effects -- physiology
Biology
Binding
Competitive

Sincalide
Arsenicals -- pharmacology
Gastrins
Acinar cell
Extracellular
Animals
Pancreas
Molecular Biology
Cholecystokinin -- metabolism
Cholecystokinin degradation
Cell Membrane
Phosphoramidon
Cell Biology
Thiorphan
Molecular biology
Rats
Pancreatic Neoplasms
Kinetics
chemistry
Pancreatic acinar cell line AR 4-2 J
Dinitrophenols
Zdroj: Biochimica et biophysica acta, 1055
ISSN: 0167-4889
DOI: 10.1016/0167-4889(90)90034-b
Popis: Cholecystokinin (CCK) receptors were investigated in the tumoral acinar cell line AR 4-2 J derived from rat pancreas, after preincubation with 20 nM dexamethasone. At steady state binding at 37°C (i.e. after a 5 min incubation), less than 10% of the radioactivity of [125I]BH-CCK-9 (3-(4-hydroxy[125I]iodophenyl)propionyl (Thr34, Nle37) CCK(31-39)) could be washed away from intact cells with an ice-cold acidic medium, suggesting high and rapid internalization-sequestration of tracer. By contrast, more than 85% of the tracer dissociated rapidly after a similar acid wash from cell membranes prelabelled at steady state. In intact AR 4-2 J cells, internalization required neither energy nor the cytoskeleton framework. Tracer internalization was reversed partly but rapidly at 37°C but slowly at 4°C. In addition, two degradation pathways of the tracer were demonstrated, one intracellular and one extracellular. Intracellular degradation occurred at 37°C but not at 20°C and resulted in progressive intracellular accumulation of [125I]BH-Arg that corresponded, after 1 h at 37° C, to 35% of the radioactivity specifically bound. This phenomenon was not inhibited by serine proteinase inhibitors and modestly only by monensin and chloroquine. Besides, tracer degradation at the external cell surface was still observable at 20°C and yielded a peptide (probably [125I]BH-Arg-Asp-Tyr(SO3H)-Thr-Gly). This degradation pathway was partly inhibited by bacitracin and phosphoramidon while thiorphan, an inhibitor of endopeptidase EC 3.4.24.11, was without effect.
info:eu-repo/semantics/published
Databáze: OpenAIRE