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- Title
Endocytosis of the somatostatin analogue, octreotide, by the proximal tubule-derived opossum kidney (OK) cell line.
- Authors
Barone, Raffaella; Van Der Smissen, Patrick; Devuyst, Olivier; Beaujean, Viviane; Pauwels, Stanislas; Courtoy, Pierre J.; Jamar, François
- Abstract
Endocytosis of the somatostatin analogue, octreotide, by the proximal tubule-derived opossum kidney (OK) cell line.Background.Nephrotoxicity of cancer therapy using radiolabeled somatostatin analogues such as octreotide is due to ultrafiltration and reuptake by proximal tubular cells (PTCs). The mechanism of uptake is unknown. It could occur either by receptor-mediated endocytosis via a somatostatin receptor or, alternatively, the multiligand megalin/cubilin tandem receptor, or by fluid-phase endocytosis. To define the mechanisms of internalization and to identify potential receptors, we have studied the uptake and processing of octreotide by the PTC-derived opossum kidney (OK) cell line.Methods.We compared the kinetics of uptake and fate of111In-diethylenetriamine pentaacetic acid (DTPA)-d-Phe1-octreotide and125I-human serum albumin (125I-HSA). To determine the contribution of receptor-mediated endocytosis, we tested competition for uptake by octreotide and somatostatin and by various megalin/cubilin ligands[receptor-associated protein (RAP), albumin, transferrin, insulin, polymixin B] or basic amino acids. The subcellular localization of fluorescein isothiocyanate (FITC)-d-Phe1-octreotide was studied by confocal microscopy.Results.Kinetics of uptake of111In-DTPA-d-Phe1-octreotide and125I-HSA by OK cells were comparable, but only the somatostatin analogue was significantly retained intact. All megalin/cubilin ligands and basic amino acids strongly inhibited125I-HSA uptake, but these could not compete for>50% of111In-DTPA-d-Phe1-octreotide uptake. The same was found for somatostatin and octreotide. The noncompetable uptake of111In-DTPA-d-Phe1-octreotide was comparable to the clearance of Lucifer Yellow, a marker of fluid-phase endocytosis. By confocal microscopy, FITC-d-Phe1-octreotide colocalized with transferrin in endosomes, then accumulated in lysosomes.Conclusion.Receptor-mediated endocytosis via megalin/cubilin and fluid-phase endocytosis contribute about equally to the uptake of radiolabeled somatostatin analogues by OK cells.
- Subjects
ENDOCYTOSIS; SOMATOSTATIN; OCTREOTIDE acetate; GASTROINTESTINAL hormones; ISLANDS of Langerhans; PEPTIDE hormones; CELL lines; CELL culture
- Publication
Kidney International, 2005, Vol 67, Issue 3, p969
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1111/j.1523-1755.2005.00160.x