Comparison of the effects of stimulators and inhibitors of resorption on the release of lysosomal enzymes and radioactive calcium from fetal bone in organ culture. [/sup 45/Ca, rats]
The release of lysosomal enzymes, collagenase, and previously incorporated /sup 45/Ca from fetal rat long bones cultured in a chemically defined medium is compared. Parathyroid hormone (PTH) and prostaglandin E/sub 2/ increased the release of ..beta..-glucuronidase, acetylglucosaminidase, and cathepsin D, but showed little effect on collagenase activity in the medium at 48 h. The dose-response relations for ..beta..-glucuronidase and /sup 45/Ca release were similar. However, the increase in lysosomal enzyme release was proportionally greater and occurred earlier than the increase in /sup 45/Ca release. PTH also caused a significant increase in total ..beta..-glucuronidase activity in bone plus medium. Several agents which stimulate /sup 45/Ca release at an optimal concentration, but not at a higher concentration, including dibutyryl cAMP, isobutylmethylxanthine, and the calcium ionophore, A23187, all increased lysosomal enzyme release at the concentration which increased /sup 45/Ca release. Three inhibitors of bone resorption (calcitonin, cortisol, and colchicine) blocked lysosomal enzyme release at the same time that /sup 45/Ca release decreased. When the bones escaped from calcitonin inhibition, both /sup 45/Ca and lysosomalenzyme release increased. While colchicine blocked both lysosomal enzymes and /sup 45/CA release, it actually increased the release of bone collagenase, and together with PTH or prostaglandin E/sub 2/ caused a large increase in free collagenase activity in the medium. These data indicate that lysosomal enzyme release is closely linked to bone resorption and suggest that lysosomal enzymes may have a primary role in initiating resorption, perhaps by acting on noncollagenous matrix or tissue components before mineral removal and collagen degradation.
- Research Organization:
- Univ. of Connecticut Health Center, Farmington
- OSTI ID:
- 6503364
- Journal Information:
- Endocrinology; (United States), Vol. 103:6
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
CALCITONIN
BIOLOGICAL EFFECTS
CALCIUM 45
METABOLISM
COLCHICINE
ENZYMES
HYDROCORTISONE
PARATHORMONE
PROSTAGLANDINS
BONE TISSUES
FETUSES
LYSOSOMES
RATS
ADRENAL HORMONES
ALKALINE EARTH ISOTOPES
ALKALOIDS
ANIMALS
ANTIMITOTIC DRUGS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CALCIUM ISOTOPES
CELL CONSTITUENTS
CONNECTIVE TISSUE
CORTICOSTEROIDS
DAYS LIVING RADIOISOTOPES
DRUGS
EVEN-ODD NUCLEI
GLUCOCORTICOIDS
HORMONES
HYDROXY COMPOUNDS
INTERMEDIATE MASS NUCLEI
ISOTOPES
KETONES
MAMMALS
NUCLEI
ORGANIC COMPOUNDS
ORGANOIDS
PEPTIDE HORMONES
PEPTIDES
POLYPEPTIDES
PREGNANES
PROTEINS
RADIOISOTOPES
RODENTS
STEROID HORMONES
STEROIDS
TISSUES
VERTEBRATES
560172* - Radiation Effects- Nuclide Kinetics & Toxicology- Animals- (-1987)