Renal metabolism of calcitonin

Journal Article · Fri Apr 01 04:00:00 EST 1988 · Am. J. Physiol.; (United States)

OSTI ID:6994489

Simmons, R E; Hjelle, J T; Mahoney, C; Deftos, L J; Lisker, W; Kato, P; Rabkin, R

The kidneys account for approximately two-thirds of the metabolism of calcitonin, but relatively little is known regarding the details thereof. To further characterize this process, we examined the renal handling and metabolism of human calcitonin (hCT) by the isolated perfused rat kidney. We also studied the degradation of radiolabeled salmon calcitonin (sCT) by subcellular fractions prepared from isolated rabbit proximal tubules. The total renal (organ) clearance of immunoreactive hCT by the isolated kidney was 1.96 +/- 0.18 ml/min. This was independent of the perfusate total calcium concentration from 5.5 to 10.2 mg/dl. Total renal clearance exceeded the glomerular filtration rate (GFR, 0.68 +/- 0.05 ml/min), indicating filtration-independent removal. Urinary calcitonin clearance as a fraction of GFR averaged 2.6%. Gel filtration chromatography of medium from isolated kidneys perfused with /sup 125/I-labeled sCT showed the principal degradation products to be low molecular weight forms eluting with monoiodotyrosine. Intermediate size products were not detected. In the subcellular fractionation experiments, when carried out at pH 5.0, calcitonin hydrolysis exclusively followed the activities of the lysosomal enzyme N-acetyl-beta-glucosaminidase. Typically, at pH 7.5, 42% of total degradation occurred in the region of the brush-border enzyme alanyl aminopeptidase and 29% occurred in the region of the cytosolic enzyme phosphoglucomutase. Although 9% of the calcitonin-degrading activity was associated with basolateral membrane fractions, most of this activity could be accounted for by the presence of brush-border membranes.

• Research Organization: Stanford Univ., CA (USA)
• OSTI ID: 6994489
• Journal Information: Am. J. Physiol.; (United States), Journal Name: Am. J. Physiol.; (United States) Vol. 254; ISSN AJPHA
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANADROMOUS FISHES
ANIMALS
AQUATIC ORGANISMS
BETA DECAY RADIOISOTOPES
BODY
CALCITONIN
CHROMATOGRAPHY
CLEARANCE
DAYS LIVING RADIOISOTOPES
ELECTRON CAPTURE RADIOISOTOPES
ENZYME ACTIVITY
ENZYMES
EXCRETION
FILTRATION
FISHES
GLYCOSYL HYDROLASES
HORMONES
HYDROLASES
IN VITRO
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KIDNEYS
KINETICS
MAMMALS
MAN
METABOLISM
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HORMONES
PEPTIDES
PERFUSED ORGANS
POLYPEPTIDES
PRIMATES
PROTEINS
RABBITS
RADIOISOTOPES
RATS
RENAL CLEARANCE
RODENTS
SALMON
SEPARATION PROCESSES
TRACER TECHNIQUES
VERTEBRATES