title: Down-regulation of calcitonin receptors in T47D cells by internalization of calcitonin-receptor complexes.
abstract: T47D cells possess specific calcitonin (CT) receptors and a CT-responsive adenylate cyclase. Internalization of part of their CT receptors has been suggested. At 37 degrees C, bound 125I-labelled salmon CT (sCT) becomes increasingly resistant to acid washing, which can remove surface-bound hormone, thus indicating internalization. Monensin and chloroquine, which raise the pH of the lysosomes and thereby inhibit cellular processing of endosomes, inhibit the decrease of total bound activity seen in the controls. Acid-resistant (internalized) activity increases to the levels of total binding. Preincubation with sCT leads to a loss of specific binding. Recovery of CT binding is prevented by monensin, which also inhibits transport of cellular proteins to the cell membrane. Recovery is not influenced by chloroquine. As chloroquine prevents recycling, we conclude that after binding of CT the receptors are internalized, transferred to a lysosomal compartment, and degraded intracellularly without recycling. All receptors seem to undergo internalization. Desensitization to CT in T47D cells is at least partly mediated by intracellular metabolism of CT receptors.
authors.affiliation: Department of Internal Medicine I, University of Heidelberg, F.R.G.
authors.forename: H G
authors.initials: HG
authors.lastname: Schneider
authors.forename: F
authors.initials: F
authors.lastname: Raue
authors.forename: A
authors.initials: A
authors.lastname: Zink
authors.forename: A
authors.initials: A
authors.lastname: Koppold
authors.forename: R
authors.initials: R
authors.lastname: Ziegler
mesh_terms: D002738:Chloroquine / Q000494:pharmacology; D005260:Female; D006801:Humans; D008985:Monensin / Q000494:pharmacology; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000648:ultrastructure*
chemical_list: D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface; D002738:Chloroquine; D008985:Monensin