Bone and parathyroid inhibitory effects of S-2(3-aminopropylamino)ethylphosphorothioic acid. Studies in experimental animals and cultured bone cells

Journal Article · Mon Apr 01 04:00:00 EST 1985 · J. Clin. Invest.; (United States)

DOI:https://doi.org/10.1172/JCI111815· OSTI ID:5123983

Attie, M F; Fallon, M D; Spar, B; Wolf, J S; Slatopolsky, E; Goldfarb, S

S-2-(3-aminopropylamino)ethylphosphorothioic acid (WR 2721) is a radio- and chemoprotective agent which produces hypocalcemia in humans. Intravenous injection of 30 mg/kg WR 2721 in rats and 15 mg/kg in dogs lowers serum calcium by 19 and 25%, respectively. Hypocalcemia in dogs is associated with a fall in serum immunoreactive parathyroid hormone (PTH), which suggests that the mechanism of its hypocalcemic effect is acute hypoparathyroidism. Despite this effect on PTH, in eight chronically parathyroidectomized rats on a low phosphate diet, WR 2721 reduced serum calcium from 9.4 to 7.7 mg/dl at 3 h. Furthermore, in dogs rendered hypercalcemic by continuous infusion of PTH, WR 2721 reduced serum calcium from 11.0 to 10.6 mg/dl. To determine whether WR 2721 causes hypocalcemia by enhancing the exit of calcium from the circulation or inhibiting its entry, the drug was infused 3 h after administration of /sup 45/Ca to rats. WR 2721 did not significantly increase the rate of disappearance of /sup 45/Ca from the circulation even though serum calcium fell by 19%. In incubations with fetal rat long bone labeled in utero with /sup 45/Ca, 10(-3) M WR 2721 inhibited PTH-stimulated, but not base-line release of /sup 45/Ca. Bone resorption by primary culture of chick osteoclasts was inhibited by WR 2721 at concentrations as low as 10(-4) M in the absence of hormonal stimulation. These studies suggest that WR 2721 lowers serum calcium predominantly by blocking calcium release from bone. This acute hypocalcemic effect is at least in part independent of its effect on the parathyroid glands, and is most likely a direct effect of the agent on bone resorption.

• Research Organization: Univ. of Pennsylvania School of Medicine, Philadelphia
• OSTI ID: 5123983
• Journal Information: J. Clin. Invest.; (United States), Journal Name: J. Clin. Invest.; (United States) Vol. 4; ISSN JCINA
• Country of Publication: United States
• Language: English

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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKALINE EARTH ISOTOPES
ALKALINE EARTH METAL COMPOUNDS
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BLOOD CHEMISTRY
BODY
BONE CELLS
CALCIUM 45
CALCIUM COMPOUNDS
CALCIUM ISOTOPES
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DISEASES
DOGS
DRUGS
ELEMENTS
ENDOCRINE DISEASES
ENDOCRINE GLANDS
EVEN-ODD NUCLEI
GLANDS
HORMONES
INHIBITION
INTERMEDIATE MASS NUCLEI
ISOTOPES
MAMMALS
NONMETALS
NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
PARATHORMONE
PARATHYROID GLANDS
PEPTIDE HORMONES
PHOSPHORUS
RADIOISOTOPES
RADIOPROTECTIVE SUBSTANCES
RATS
RODENTS
SOMATIC CELLS
THIOIC ACIDS
VERTEBRATES