Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A variety of analogs of 1,25-(OH)2D3 with less calcemic activity and lower receptor binding affinity than 1,25-(OH)2D3 have been developed. However, these compounds have equal or greater ability to differentiate leukemia cells and psoriatic fibroblasts and to suppress PTH synthesis and secretion. The mechanism for this selectivity has not been elucidated. Because the lower potency of ergocalciferol compared to cholecalciferol in preventing or curing rickets in chicks was associated with a lower affinity of the avian vitamin D binding protein (DBP) for vitamin D2, we tested five analogs with low calcemic activity including 22-oxa-1,25-(OH)2D3 (OCT), MC903, 1,25-(OH)2-16 ene-23-yne D3, 1,25-(OH)2-26,27 dihomo-22-ene-D3, and 1,25-(OH)2-24-trihomo-22-ene-D3 for their affinity for rat serum DBP. All analogs had a low affinity for DBP, ranging from 50-3000 times less than that of 1,25-(OH)2D3. OCT also bound with low affinity to dog and human serum DBP. We tested with OCT the possible consequences of its low affinity for serum DBP. One of the functions of DBP is to prolong the lifetime of 1,25-(OH)2D3 in circulation. Quantification of the metabolic clearance rate (MCR) of OCT in 8 normal dogs using a single bolus injection technique showed that OCT was cleared at a rate of 48.2 +/- 7.5 ml/min, approximately 6-7 times more rapidly than 1,25-(OH)2D3 (6.8 +/- 0.4 ml/min). The estimated half-life of OCT in the circulation was 2.5 +/- 0.3 h compared to 7.0 +/- 0.6; n = 7 for 1,25-(OH)2D3. As our primary interest is the potential of OCT in treating the secondary hyperparathyroidism of CRF, we also measured the MCR of OCT in 5/6 nephrectomized dogs. Uremia does not affect the rate of clearance of OCT from the circulation (MCR: 56.8 +/- 4.5; t1/2 = 2.1 +/- 0.2 n = 4). Despite its shorter half-life, OCT suppressed PTH secretion in vivo in uremic dogs. The effects of low binding to DBP on the percentage uremic dogs. The effects of low binding to DBP on the percentage of free sterol were determined using an ultrafiltration procedure. We compared the proportion of free (unbound) OCT and 1,25-(OH)2D3 in 0.1% BSA-PBS with concentrations of human serum ranging from 0-25%. The proportion of OCT in the free form was significantly higher than that of 1,25-(OH)2D3 for every serum concentration tested. The physiological relevance of a higher percentage of free OCT was tested in normal human macrophages.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:On the mechanisms for the selective action of vitamin D analogs. 200 95

PTH is a potent bone anabolic factor, and its combination with antiresorptive agents has been proposed as a therapy for osteoporosis. We tested the effects of PTH, alone and in combination with the novel antiresorptive agent OPG, in a rat model of severe osteopenia. Sprague Dawley rats were sham-operated or ovariectomized at 3 months of age. Rats were untreated for 15 months, at which time ovariectomy had caused significant decreases in bone mineral density in the lumbar vertebrae and femur. Rats were then treated for 5.5 months with vehicle (PBS), human PTH-(1-34) (80 microg/kg), rat OPG (10 mg/kg), or OPG plus PTH (all three times per wk, sc). Treatment of ovariectomized rats with OPG or PTH alone increased bone mineral density in the lumbar vertebrae and femur, whereas PTH plus OPG caused significantly greater and more rapid increases than either therapy alone (P < 0.05). OPG significantly reduced osteoclast surface in the lumbar vertebrae and femur (P < 0.05 vs. sham or ovariectomized), but had no effect on osteoblast surface at either site. Ovariectomy significantly decreased the mechanical strength of the lumbar vertebrae and femur. In the lumbar vertebrae, OPG plus PTH was significantly more effective than PTH alone at reversing ovariectomy-induced deficits in stiffness and elastic modulus. These data suggest that OPG plus PTH represent a potentially useful therapeutic option for patients with severe osteoporosis.
 ...
PMID:OPG and PTH-(1-34) have additive effects on bone density and mechanical strength in osteopenic ovariectomized rats. 1156 87

We successfully established a novel cell line (OS-1) derived from human ovarian small cell carcinoma, hypercalcemic type secreted PTH, PTH-rP and ACTH. The OS-1 cell line was established from metastatic focus of uterus. A patient was 25-year-old Japanese woman. The first she received left ovariectomy on April 2002. The histopathological diagnosis was ovarian small cell carcinoma, pT2c, Nx, Mx. Then on June 2003, metastatic focus of uterus was ectomied. A part of the recurrent tumor of uterus was cut into small pieces with razor blades, and dissociated with 0.1% trypsin-0.02% EDTA/ PBS(-) solution at room temperature. The single cells and small cell clusters were seeded into 60mm dishes and cultured in growth medium (GM: DMEM/F12 supplemented with 20% fetal bovine serum and 0.1% non-essential amino acids solution) at 37 degrees C, 4.7% CO2 in humidified air. Medium was exchanged twice a week. The OS-1 cells grew as floating cultures in the dishes. Radioimmunoassay of the conditioned media was revealed that the cultures secreted large amount of PTH, PTHrP and ACTH simultaneously. Susceptibilities of anti-cancer drugs to the OS-1 cells were examined using oxygen electrode meter (Daikin), and the results suggested VLB and TXL were effective, and CDDP, CPT-11, VP-16, VCR, CPA, MMC and CBDCA were not effective. In our knowledge, it is the first report that the cell line secreting PTH, PTHrP and ACTH was successfully established from ovarian small cell carcinoma, hypercalcemic type. We expect that OS-1 cell line contribute to study on the mechanism of ectopic hormone secretion and susceptibility of anti cancer drugs to the small cell carcinoma.
 ...
PMID:Establishment and characterization of a human ovarian small cell carcinoma, hypercalcemic type, cell line (OS-1) secreting PTH, PthrP and ACTH--special reference to the susceptibility of anti-cancer drugs. 1603 5