Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In UMR 106 rat osteosarcoma cells, parathormone (1-34hPTH) and calcitonin (sCT) stimulated adenylate cyclase (AC) activity 5.5-and 2.8-fold, respectively. AC in osteoblasts (OB) from collagenase-treated calvaria of 3-day-old rats responded similarly to 1-34hPTH. In contrast, fibroblasts (mouse fibroblastomas) displayed a marginal 1-34hPTH sensitive AC. Osteoclasts (OC) of collagenase-treated rat calvariae, rat monocytes and mouse macrophages did not demonstrate 1-34hPTH inducable AC activity. Physiological concentrations of 24,25-dihydroxyvitamin D-3 attenuated PTH-sensitive AC in OB and UMR 106 cells within 20 min, while 1,25-dihydroxyvitamin D-3 showed no such immediate effect. In contrast, the AC response to Gpp(NH)p was unaffected by 24,25-(OH)2D3, indicating that 24,25-(OH)2D3 interrupts the coupling of the PTH receptor to the GTP binding protein Gs. OB and UMR 106 cells were also subjected to long-term (48 h) incubation with vitamin D-3 metabolites, 1-34hPTH or 20% serum from patients with secondary hyperparathyroidism (sHBT-serum), respectively. PTH-sensitive AC was markedly attenuated by pre-exposure to both 1-34hPTH and 1,25-(OH)2D3, while minimally affected by corresponding 24,25-(OH)2D3 and 20% sHPT-serum treatment. The secretion of alkaline phosphatase (Alphos) from the two cell types was strongly increased by 1-34hPTH, the effect being abolished by the presence of 24,25-(OH)2D3. Iliac crest biopsies of normal individuals exhibited a clear negative correlation between PTH-sensitive AC and corresponding serum 24,25-(OH)2D3 levels. Basal AC activity was, however, negatively correlated to serum 1,25-(OH)2D3 concentrations. In summary, the results show that 24,25-(OH)2D3 reduces PTH-stimulated AC activity in and Alphos secretion from osteoblastic bone cells by rapidly and directly interfering with the plasma membrane. These data reinforce the probable in vivo significance of 24,25-(OH)2D3. Moreover, the negative correlation between basal AC activity and serum 1,25-(OH)2D3 levels indicates a possible role for 1,25-(OH)2D3 in regulating bone cell synthesis of AC components in vivo.
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PMID:1,25-dihydroxyvitamin D-3 and 24,25-dihydroxyvitamin D-3 affect parathormone (PTH) -sensitive adenylate cyclase activity and alkaline phosphatase secretion of osteoblastic cells through different mechanisms of action. 216 95

Of the total urinary hydroxyproline in normal subjects and those with skeletal disorders, between 4 and 20% was nondialyzable. In some patients with Paget's disease of bone, hyperparathyroidism with osteitis fibrosa, hyperphosphatasia, and extensive fibrous dysplasia the total urinary hydroxyproline was sufficiently high to permit purification of this polypeptide hydroxyproline by gel filtration and ion exchange chromatography. The partially purified polypeptides had molecular weights between 4500 and 10,000 and amino acid compositions and physical properties resembling those of gelatin. The polypeptide fractions also contained neutral sugar and glucosamine. These fragments had been shown to be susceptible to cleavage by purified bacterial collagenase suggesting the presence of the sequence-Pro-X-Gly-Pro-Y-. After administration of proline-(14)C to patients with Paget's disease hydroxyproline-(14)C was excreted in the urine. The hydroxyproline-(14)C specific activity reached a peak in 2-4 hr and declined rapidly. The specific activity of the polypeptide (retentate) portion was severalfold greater than that of the raw urine and diffusate. When the labeled urines were subjected to gel filtration the hydroxyproline-(14)C fractions of highest molecular weight which were eluted first from the columns had the highest specific activities. Exposure of the hydroxyproline-(14)C-containing polypeptides to bacterial collagenase rendered them dialyzable. Four patients with hyperparathyroidism and osteitis fibrosa were studied before and after removal of a parathyroid adenoma, a period of transition from a predominance of bone collagen resorption to one of relatively increased bone collagen synthesis. The total urinary hydroxyproline fell rapidly after operation whereas the ratio of the polypeptide fraction to the total rose three- to fourfold. The results of these studies suggest that the urinary polypeptides represent fragments of collagen related to collagen synthesis. Changes in the ratio of these peptides to total hydroxyproline in the urine may serve as an index of new bone formation in patients with skeletal disorders.
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PMID:Urinary polypeptides related to collagen synthesis. 431 4

Allotransplantation of microencapsulated parathyroid tissue is a promising approach to the treatment of permanent hypoparathyroidism. Preoperative assessment of the quality of microencapsulated parathyroid tissue could facilitate selection of the optimal bioartifical graft for human parathyroid allotransplantation. Parathyroid tissue from patients with secondary hyperparathyroidism (n = 15) was processed mechanically or enzymatically (collagenase type II). Tissue particles and single cells/cell clusters were routinely microencapsulated with amitogenic Ba(2+) alginate. Parathyroid secretion dynamics in response to stimulation of nonencapsulated and microencapsulated parathyroid tissue with Ca(2+) were evaluated in a perifusion system. The stability of the different types of microcapsule was assessed using an osmotic pressure test. Mechanical cutting of parathyroid tissue led to peripheral necrosis of tissue particles and impaired their vitality. Collagenase digestion, in contrast, resulted in single cells and cell clusters without peripheral necrosis. The quality of microencapsulation of single cells/cell clusters was significantly better than that of tissue particles (deformed and imperfect capsules). Microencapsulation itself did not decrease cell vitality. Nonencapsulated and microencapsulated tissue particles and single cells/cell clusters from different donors maintained their own levels of response to stimulation with low Ca(2+). Microcapsules containing tissue particles showed poor stability compared with those containing single cells/cell clusters. Preoperative evaluation of microencapsulated parathyroid tissue can disclose differences in vitality and function and thus facilitate selection of the optimal bioartifical graft for human parathyroid allotransplantation.
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PMID:Preoperative evaluation of microencapsulated human parathyroid tissue aids selection of the optimal bioartificial graft for human parathyroid allotransplantation. 1751 31

It has been shown previously that the antisecretory response of famotidine (histamine H2-receptor antagonist) is altered in patients with renal failure. To evaluate the underlying mechanism(s) of this clinical observation we obtained biopsy specimens of fundic mucosa from two groups of patients with variable renal function (group 1 normal renal function (n = 8); group 2 renal insufficiency (n = 8), CL(CR) < 20 mL/min) [matched for age and sex]. Furthermore, we investigated the effect of intact parathyroid hormone (PTH (1-84)), urea and calcium on 14C-aminopyrine uptake as an indicator of acid secretion. Gastric mucosal cells from human biopsies were isolated by pronase and collagenase digestion. Cyclic AMP content of parietal cells was determined by radioimmunoassay. Histamine and calcium stimulated 14C-aminopyrine uptake. PTH (1-84) suppressed basal 14C-aminopyrine accumulation, whereas addition of urea had no influence either in presence or in absence of histamine. In contrast to histamine, PTH (1-84) did not induce a significant increase in cellular cyclic AMP. In conclusion, there is no difference in the activation of 14C-aminopyrine uptake between patients with normal renal function and renal insufficiency except lower basal values in patients with renal failure. This could be caused by PTH (1-84) and urea which inhibit gastric acid secretion. Only calcium is the important agent causing an increase in the sensitivity of parietal cells in hyperparathyroidism.
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PMID:Influence of chronic renal failure on acid secretion in isolated gastric mucosal cells from human biopsies. 2038 Mar 54