Down-regulation of rat kidney calcitonin receptors by salmon calcitonin infusion evidence by autoradiography

Journal Article · Sat Aug 01 00:00:00 EDT 1987 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.84.15.5125· OSTI ID:5294086

Bouizar, Z; Rostene, W H; Milhaud, G

In treating age-related osteoporosis and Paget disease of bone, it is of major importance to avoid an escape phenomenon that would reduce effectiveness of the treatment. The factors involved in the loss of therapeutic efficacy with administration of large pharmacological doses of the hormone require special consideration. Down-regulation of the hormone receptors could account for the escape phenomenon. Specific binding sites for salmon calcitonin (sCT) were characterized and localized by autoradiography on rat kidney sections incubated with /sup 125/I-labeled sCT. Autoradiograms demonstrated a heterogeneous distribution of /sup 125/I-labeled sCT binding sites in the kidney, with high densities in both the superficial layer of the cortex and the outer medulla. Infusion of different doses of unlabeled sCT by means of Alzet minipumps for 7 days produced rapid changes in plasma calcium, phosphate, and magnesium levels, which were no longer observed after 2 or 6 days of treatment. Besides, infusion of high doses of sCT induced down-regulation of renal sCT binding sites located mainly in the medulla, where calcitonin (CT) has been shown to exert it physiological effects on water and ion reabsorption. These data suggest that the resistance to high doses of sCT often observed during long-term treatment of patients may be the consequence of not only bone-cell desensitization but also down-regulation of CT-sensitive kidney receptor sites.

• Research Organization: Centre Hospitalier Universitaire Saint-Antoine, Paris (France)
• OSTI ID: 5294086
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 84:15; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMALS
AUTORADIOGRAPHY
BETA DECAY RADIOISOTOPES
BLOOD CHEMISTRY
BODY
CALCITONIN
DAYS LIVING RADIOISOTOPES
ELECTRON CAPTURE RADIOISOTOPES
HORMONES
INFUSION
INTAKE
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KIDNEYS
MAMMALS
MEMBRANE PROTEINS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HORMONES
PEPTIDES
POLYPEPTIDES
PROTEINS
RADIOISOTOPES
RADIORECEPTOR ASSAY
RATS
RECEPTORS
RODENTS
TRACER TECHNIQUES
VERTEBRATES