Renal metabolism of calcitonin.
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Simmons RE, Hjelle JT, Mahoney C, Deftos LJ, Lisker W, Kato P, Rabkin R
Renal metabolism of calcitonin.
Am J Physiol. 1988 Apr;254(4 Pt 2):F593-600. doi: 10.1152/ajprenal.1988.254.4.F593.
- PubMed ID
- 2833122 [ View in PubMed]
- Abstract
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 125I-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.(ABSTRACT TRUNCATED AT 250 WORDS)
DrugBank Data that Cites this Article
- Drugs
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Human calcitonin Alpha-N-acetylglucosaminidase Protein Humans NoSubstrateDetails Human calcitonin Aminopeptidase N Protein Humans NoSubstrateDetails Human calcitonin Phosphoglucomutase-1 Protein Humans NoSubstrateDetails