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P Esbrit

Publications and source records attributed to P Esbrit.

At least 19 recordsLinked to original sources
PubMed1992

Isolation of a 18,000-Da molecular weight form of parathyroid hormone-related protein from the rat Walker carcinosarcoma 256.

The hypercalcaemic Walker carcinosarcoma 256 is a rat model for humoral hypercalcaemia of malignancy (HHM). Tumour products such as parathyroid hormone-related proteins (PTHRP) and various growth factors appear to be responsible for this syndrome. Recently, PTHRP immunoreactivity has been detected in the conditioned medium of Walker tumour cells. The present report describes the isolation of a 18,000-Da molecular weight form of PTHRP from Walker tumour homogenates, by using a relatively simple immunoaffinity purification method. Our results suggest that this PTHRP form is similar to that purified from other HHM-related tumours.

Animals↗
PubMed1992

Role of kidney and liver in the renotropic activity generated in rats after uninephrectomy.

Following uninephrectomy the remnant kidney undergoes a compensatory growth apparently regulated by a humoral renotropic factor(s). Our studies were carried out to assess the role of renal and hepatic tissue in the generation of such a renotropic factor(s). The renotropic activity in extracts of rat kidney and liver obtained at different times after uninephrectomy was assayed in cortical tubules from rat kidney removed 24 h after uninephrectomy. We found that kidney extracts from 6 h and 24 h uninephrectomized rats increased [3H]thymidine incorporation into tubular cell DNA, dose-dependently, compared to those from sham-operated rats. Maximal stimulation was observed at 10(4)-fold (6 h) or 10(2)-fold (24 h) extract dilution. This activity was undetected in perfused kidney extracts, or in extracts of kidneys from simultaneously uninephrectomized and partially hepatectomized rats. However, only 10-fold dilution of unperfused liver extract from 6 h or 24 h uninephrectomized rats showed significant activity. Kidney or liver extracts from 30 min uninephrectomized animals failed to display activity. Our results point to an extrarenal origin for the humoral renotropic activity generated after uninephrectomy, although the kidney seems to modulate this activity.

Animals↗
PubMed1991

Relative role of bone and kidney in the hypercalcaemia associated with the rat Walker carcinosarcoma 256.

The rat Walker carcinosarcoma 256 is an animal model for humoral hypercalcaemia of malignancy (HHM). In this model, the relative contribution of bone and kidney in the hypercalcaemia of tumour-bearing rats was investigated. Daily administration of pamidronate, a bone resorption inhibitor, for 2 days prevented the increased fasting Ca2+ excretion observed in the hypercalcaemic rats, although serum Ca2+ remained high. However, the high serum Ca2+ normalised after the acute injection of ethiofos, an inhibitor of renal Ca2+ reabsorption, which was associated with a marked increase of Ca2+ excretion. Changes in Ca2+ were accompanied by similar changes in Mg2+. The results indicate that altered renal Ca2+ handling has a key role in the hypercalcaemia associated with this HHM model.

Amifostine↗
PubMed1991

Co-purification of calcium transport-stimulating and DNA synthesis-stimulating agents with parathormone-like activity isolated from the hypercalcaemic strain of the Walker 256 tumour.

One of the strains of the Walker 256 carcinosarcoma induces in the rat a humoral hypercalcaemia of malignancy (HHM) syndrome which is similar to that reported in human patients. We have isolated from this tumour a chromatographic fraction which displays an adenylate cyclase stimulating activity in dog kidney cortical membranes, similar to that of a parathormone (PTH) related protein isolated from various HHM related tumours. In addition, this fraction stimulated initial calcium (Ca) uptake in confluent Madin-Darby canine kidney (MDCK) cell monolayers in a dose-dependent manner. Maximal stimulation of Ca uptake was associated with an enhanced Ca efflux from MDCK cells preloaded with the cation, and with an increased DNA synthesis in these cells. These activities might be involved in development of increased tubular calcium reabsorption in Walker 256 tumour-bearing rats.

Adenylyl Cyclases↗
PubMed1990

Evidence of 1,25-dihydroxyvitamin D synthesis by the rat Walker carcinosarcoma 256.

We tested the existence of 25-hydroxyvitamin D-1 alpha-hydroxylase activity in the Walker carcinosarcoma 256 implanted in rats. This tumour has been shown to induce hypercalcaemia in the host animal. We found this enzyme activity in tumour homogenates, which was in the same range as that in the kidney of tumour-bearing rats. Our results suggest that 1,25-dihydroxyvitamin D synthesized by the Walker tumour might be involved in the mechanism responsible for the hypercalcaemia in the host rat.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1989

Partial purification and characterisation of a renal growth factor from plasma of uninephrectomised rats.

Renal growth factor activity was extracted from plasma of adult uninephrectomised rats and partially purified by gel filtration and anion-exchanger FPLC. It induced a maximal stimulation of mouse DNA synthesis in vivo at 1.75 micrograms/mouse. In addition, renal growth factor was found to maximally stimulate DNA synthesis in LLC-PK1 cells at 150 ng/ml. This maximal response was then found to decrease with higher doses of renal growth factor, in vivo and in vitro. The apparent molecular weight of renal growth factor was estimated to be 17K-22 K by gel filtration. It was found to be resistant to heat and to trypsin, but labile to reduction with dithiothreitol.

Animals↗
PubMed1989

Lipid methylation, hormone action and compensatory hypertrophy in renal cortical tubules.

Lipid methylation has been studied in homogenized dog kidney cortical tubules. At pH 9, using S-adenosyl-L-methionine as methyl donor, most of the methyl groups appeared incorporated into phosphatidylcholine, the activity showing an apparent Km of 16 microM. This enzymatic activity was unchanged by the presence of the divalent cations Ca2+ or Mg2+, cAMP or cGMP. In addition, lipid methylation was also unchanged after treatment of intact tubules with angiotensin II, parathyroid hormone or vasopressin. An increased phosphatidylcholine synthesis was observed in the remnant kidney cortical tubules after uninephrectomy through an activation of phosphocholine transferase without detectable modification of lipid methylation. These findings suggest that lipid methylation is not regulated by these biochemical or functional stimuli tested in canine renal cortical tubules.

Animals↗
PubMed1988

Compensatory changes in calcium uptake and phospholipid composition in rat renal brush border membranes after unilateral nephrectomy.

Unilateral nephrectomy (uNX) induces a decrease in calcium uptake by brush border membranes (BBM) in the remnant kidney compared to control membranes. This effect was found to occur within 48 h and persisted at 2 weeks after uNX. Moreover, this decreased calcium uptake appears to occur through a diminished binding capacity of the BBM. Our studies also show that renal hypertrophy induced a specific decrease in the content of acidic phospholipids in remnant kidney BBM by 48 h after uNX. The decrease in phosphatidylinositol 4,5-bisphosphate and phosphatidic acid was transitory but phosphatidylinositol 4-monophosphate levels remained lower in the BBM at 2 weeks after uNX compared to control membranes. These results suggest that the decreased calcium uptake by remnant kidney BBM after uNX is related to a decreased membrane content of acidic phospholipids. This effect might account, at least in part, for the decrease in fractional calcium reabsorption during renal compensatory hypertrophy.

Animals↗
PubMed1988

A possible mechanism whereby parathyroid hormone stimulates phospholipid synthesis in canine renal tubules.

Incubation of canine renal cortical tubules with parathyroid hormone and [3H]glycerol stimulated incorporation of tracer into phosphatidylinositol 4-phosphate and decreased phosphatidic acid labelling but did not affect phosphatidylinositol, phosphatidylcholine/phosphatidylserine, phosphatidylethanolamine/phosphatidylglycerol, 1,2-diacyl- or triacylglycerol labelling. The hormone did not change the activity of glycerol 3-phosphate acyltransferase or of phosphatidate phosphohydrolase measured in tubule homogenates. However, parathyroid hormone induced a rapid increase in phosphatidylinositol kinase activity associated with a decrease in Km of the enzyme for ATP in homogenized tubules. These findings suggest a possible mechanism whereby parathyroid hormone increases phospholipid synthesis in the renal cortex.

1-Phosphatidylinositol 4-Kinase↗
PubMed1987

Stimulation of inositol trisphosphate and diacylglycerol production in renal tubular cells by parathyroid hormone.

Parathyroid hormone (PTH) produced a dose-dependent immediate stimulation of inositol triphosphate and diacylglycerol production in the opossum kidney cell line, primary culture proximal tubular cells, and basolateral membranes from canine proximal tubular segments. The increase in inositol triphosphate production was accompanied by a minor increase in inositol phosphate and no significant increase in inositol bisphosphate production. Associated with the changes in inositol triphosphate and diacylglycerol, there was an immediate hydrolysis of phosphatidylinositol 4'5-bisphosphate. The effect on phospholipid hydrolysis was followed by stimulation of phosphorylation of phosphatidylinositol 4' monophosphate and phosphatidylinositol. PTH produced a sudden increase in cytoplasmic Ca2+ in opossum kidney cells that persisted for approximately 1 min. Inositol triphosphate transiently increased cytoplasmic Ca2+ in saponin-treated opossum kidney and primary culture proximal tubule cells. The effects of PTH were not mimicked by cyclic nucleotides. In fact, cyclic AMP appeared to diminish inositol triphosphate production. These results demonstrate that PTH may activate renal tubular epithelial cells by the production of inositol triphosphate and diacylglycerol.

Animals↗
PubMed1987

[Perfusion of the dog tibia isolated for the study of mineral metabolism].

A method for perfusion of isolated canine tibia is described. With this procedure the influence of different albumins on the uptake of tritiated 25-hydroxyvitamin D3 (3H-25(OH)D3) by the tibia has been studied. Bovine serum albumin at 1% concentration seems to be optimum for this system. This experimental approach seems to be useful for the study of mineral metabolism.

Animals↗