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Biomedical subjects

B Escoubet

Publications and source records attributed to B Escoubet.

13 recordsLinked to original sources
PubMed1992

Phosphate transport by fibroblasts from patients with hypophosphataemic vitamin D-resistant rickets.

It is accepted that renal phosphate wasting is the basis of hypophosphataemia in vitamin D-resistant hypophosphataemic rickets (VDRR). Abnormal renal adaptation to phosphate deprivation has also been reported in these patients. We studied sodium-dependent phosphate transport and its modulation by phosphate deprivation in skin fibroblasts cultured from healthy subjects and patients with VDRR. Control fibroblasts exhibited high-affinity sodium-dependent phosphate transport (77 +/- 12 mumol/l) which resembled the ubiquitous transport of renal and non-renal cells. Phosphate deprivation (incubation in low phosphate medium) increased the maximal velocity (Vmax) of the transport by 2.7-fold after 24 h, with no change in the affinity. The increase in Vmax was dependent on gene transcription and protein synthesis. The sodium-dependent phosphate transport exhibited in fibroblasts from VDRR patients did not significantly differ from that of control subjects, except that the Vmax of the phosphate transport was higher in cells from patients with VDRR under normal and phosphate-deprivation conditions, although the difference was significant only after 24 h of phosphate deprivation (Vmax: 22.6 +/- 2.4 pmol/mg protein per s in VDRR vs 16 +/- 3.6 pmol/mg protein per s in controls, P less than 0.05). These data demonstrate that sodium-coupled phosphate transport in human skin fibroblasts has the properties of ubiquitous sodium-phosphate co-transport and show that this transport is not deficient in patients with VDRR. Indeed paradoxically the Vmax was 40% higher in VDRR than in control subjects after 24 h of phosphate deprivation. The transport must be either different from that of kidney cells responsible for the phosphate leak, or differently modulated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

[Hypophosphatemia of a genetic origin].

Familial hypophosphatemia are either primitive disorders of renal phosphate handling, isolated as in X linked hypophosphatemic rickets (XLHR) or associated with alterations of renal handling of other solutes. They can also occur in the course of a number of other inherited diseases such as vitamin D dependent rickets type I or II and distal tubular acidosis. The molecular basis of most of these diseases are unknown. Chronic hypophosphatemia induces an alteration of bone mineralisation with rickets in children and osteomalacia in children and adults. Hypophosphatemia and the bone disease are most important in XLHR or VDDR. Treatment with oral phosphate and 1 alpha hydroxylated vitamin D metabolites, and in some cases calcium, tends to correct the hypophosphatemia and the bone disease. Treatment of the associated metabolic disorder in certain Fanconi syndromes can correct hypophosphatemia. In the forms associated with hypocalcemia, phosphate therapy is not indicated, but rather calcium therapy.

Adult↗
PubMed1991

PKC and Pi deprivation modulate differently the ubiquitous Na-dependent Pi uptake in MDCK cells.

The role of protein kinase C (PKC) in the modulation of the ubiquitous sodium-dependent phosphate transport and in adaptation of that transport to phosphate deprivation was investigated in MDCK cells. Phorbol myristate acetate (PMA) had a biphasic effect on sodium-dependent phosphate uptake characterized by early inhibition (-25% at 1 h) followed by late stimulation (2.3-fold at 15 h). Late stimulation was related to a decreased apparent affinity (Km) with unchanged maximal velocity (Vmax). The 15-h stimulation of phosphate uptake was also induced by an initial 1-h PMA treatment followed by a 14-h washout of PMA or by R59 022. The stimulation was inhibited by PKC downregulation. PMA stimulation was dependent on protein synthesis but not on transcription, as shown by the respective effects of cycloheximide, 3'-deoxyadenosine, and actinomycin D. In phosphate-deprived cells PMA had also a biphasic effect. A potentiation of PMA stimulation of phosphate uptake with phosphate deprivation was observed. Adaptation to phosphate deprivation was not prevented by PKC downregulation. Cytosolic and membranous PKC activities were not changed by 15-h phosphate deprivation. We conclude that 1) PKC modulates sodium-dependent phosphate uptake in MDCK cells, and 2) phosphate deprivation and PKC modulation of sodium-dependent phosphate uptake involve different cellular pathways; that is, phosphate deprivation acts through gene regulation, and PKC acts through translation regulation.

Adaptation, Physiological↗
PubMed1989

Adaptation to Pi deprivation of cell Na-dependent Pi uptake: a widespread process.

Phosphate enters kidney proximal tubular cells through an apical sodium-phosphate cotransport; this activity (Vmax) increases during phosphate deprivation (Kidney Int. 18: 36-47, 1980). This study investigated the mechanism of phosphate uptake and its adaptation to phosphate deprivation in cultured cells from different origins (kidney, LLC-PK1 and MDCK cells; liver, Fao cells; heart, myocyte primary cultures). All cells exhibited a sodium-dependent phosphate uptake that was reduced (greater than 75%) by external sodium substitution and inhibited by ouabain (35%) and 2,4-dinitrophenol or KCN (80%). Phosphate deprivation (exposure to phosphate-free medium) increased sodium-dependent phosphate uptake by 1.8- to 5.8-fold and decreased cell inorganic phosphate and ATP contents (70-80 and 17-30%, respectively). The stimulation of phosphate uptake resulted from an increase in Vmax without change in Km and was dependent on gene transcription and protein synthesis because it was inhibited by cycloheximide and 3-deoxyadenosine. Thus a deprivation-stimulated, sodium-dependent phosphate transport was demonstrated in cells originating from distal kidney tubules, liver, and heart. The findings suggest that in hypophosphatemic diseases, impairment of renal proximal phosphate reabsorption might be only one expression of a widespread alteration of cell phosphate regulation.

Alanine↗
PubMed1989

Effects of lidocaine on sarcolemmal fluidity and cellular cAMP in rat cardiomyocytes.

Antiarrhythmic drugs with local anesthetic properties modify the physical state of membrane phospholipids and could change adenylate cyclase activity and, thus, influence cardiac ischemic arrhythmias. Adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in cardiomyocytes cultured from newborn rat and fluorescence anisotropy of sarcolemma-enriched membranes were investigated in the presence of a neutral anesthetic drug benzyl alcohol and of a cationic anesthetic drug lidocaine. Benzyl alcohol increased in a dose-dependent manner both sarcolemma fluidity and isoproterenol- or cholera toxin-stimulated cAMP accumulation. In contrast, benzyl alcohol inhibited cAMP accumulation in forskolin-stimulated cells. Lidocaine induced a dose-related inhibition of isoproterenol-, forskolin-, and cholera toxin-stimulated cAMP accumulation without eliciting any change in sarcolemma fluidity. The inhibitory effect of lidocaine on isoproterenol-stimulated cAMP accumulation was reversed when cells were pretreated with pertussis toxin. These data suggest that the inhibitory effect of lidocaine on cAMP synthesis might involve a polar interaction with the Gi regulatory subunit of adenylate cyclase. Such an effect could contribute, in vivo, to both the antiarrhythmic and the negative inotropic effect of lidocaine.

Adenylate Cyclase Toxin↗
PubMed1987

Prostaglandin synthesis and membrane fatty acid composition in the heart of obese Zucker rats.

Genetically obese Zucker rats share several abnormalities with obese patients: inheritance of the obesity, hyperinsulinemia, hypertriglyceridemia. Because alterations in membrane fatty acid composition and in prostaglandin synthesis can be involved in the genesis of the cardiovascular complications of obesity, cardiac prostaglandins and phospholipid fatty acid composition were compared in obese and lean animals. Obese cardiac tissues produced smaller amounts of prostacyclin, thromboxane A2 and PGE2 than lean (p less than 0.01). The cyclooxygenase pathway and the activation of phospholipase by the calcium ionophore A 23187 were not altered. Phospholipid fatty acid composition of obese tissues was abnormal: the amount of stearic, arachidonic, docosapentaenoic and cervonic acids was decreased, whereas the amount of linoleic acid, the precursor of arachidonic acid, was doubled. It is concluded that obesity in Zucker rats is associated with alteration of cardiac arachidonic acid metabolism and that the alterations associated with obesity can be studied in this rat strain.

Animals↗
PubMed1987

Prostaglandins in the semicircular canal of the frog.

The synthesis of prostaglandins by ampulla and duct tissue isolated from the frog posterior semicircular canal was investigated in vitro. Ampulla and duct produced PGE2 (9 and 6 pg/structure, respectively) and prostacyclin (26 and 12 pg/structure). In the ampulla, prostaglandins mostly originated from the part containing dark and sensory cells and was not altered by 10(-3) M streptomycin. Prostaglandin levels were time-dependent and temperature-dependent. Arachidonic acid (3 X 10(-5) M) stimulated PGI2 synthesis by ampulla and duct (by 11.4 and 17 times) and PGE2 synthesis by 50 times in both structures. Ionophore A23187 stimulated ampulla and duct PGI2 synthesis (by 4.8 and 5.6 times) and PGE2 synthesis (by 2.4 and 1.8 times). Subcutaneous 100 mg/kg aspirin reduced PGI2 and PGE2 synthesis (ampulla: -87%, -33%; duct: -100%, -33%). Indomethacin (10(-6) M), in vitro, decreased PGI2 and PGE2 synthesis (ampulla: -47%, -47%; duct; -22%, -77%). Within 3 h, aspirin (5 X 10(-6) M) or arachidonic acid (2 X 10(-5) M) did not change Na and K concentrations in endolymph. It is concluded that frog inner ear produces PGI2 and PGE2, mostly from the part containing the dark cells, and that prostaglandins could be involved in the physiology of inner ear.

Animals↗
PubMed1986

Verapamil depresses the synthesis of lipoxygenase products by hypoxic cardiac rat fibroblasts in culture.

Lipoxygenase metabolites of arachidonic acid are potent chemotactic and vasoconstrictive agents and their local production in the myocardium induces the migration of polymorphonuclear cells into ischemic myocardium. These cells have been shown to play a role in the development of ischemic myocardial lesions. In the present study, the synthesis of arachidonic acid lipoxygenase metabolites by rat cardiac cells in culture and the effect of verapamil were investigated under normal and hypoxic conditions. Myocytes and fibroblasts metabolized exogenous arachidonic acid into 12-HETE and an unidentified metabolite (X). Fibroblasts synthesized significantly greater amounts of 12-HETE than myocytes (P less than 0.01). Hypoxia (glucose-free medium and low PO2) and verapamil (10(-7) M) under normal conditions, did not change metabolite synthesis by either type of cells. Under hypoxia, verapamil decreased significantly 12-HETE and X production by fibroblasts (P less than 0.01 and P less than 0.05), whereas the synthesis in myocytes was not changed. It is concluded that the decrease in lipoxygenase product synthesis under hypoxia by verapamil may contribute to its therapeutic effects on the ischemic heart.

Anaerobiosis↗
PubMed1979

[Vascular endothelium (author's transl)].

Studies during recent years have shown the importance of the vascular endothelium in several physiological and pathological circumstances. The culture of endothelial cells has permitted the direct study of endothelial functions. The endothelium is a selective barrier between blood and tissues: the molecules cross it, according to their size, either through the intercellular junctions or through the cells by pinocytotic vesicles. The permeability is modulated by vasomotor agents and modified during endothelial regeneration, especially for the lipids. The endothelium plays a prominent part in the maintenance of the blood flow through its nonthrombogenic properties. It metabolizes circulating thrombogenic substances (arachidonic acid, adenosine diphosphate) and produces potent antiaggregating agents (prostacyclin and adenosine). It may also release a plasminogen activator promoting thrombolysis. The endothelial cells contribute to the formation of the basement membrane by synthesizing collagen and fibronectin, which are involved in platelet adhesion and aggregation to exposed subendothelium. On the other hand, the endothelium has a modulating influence on the local blood flow by producing vasoconstrictors (angiotensin II and III) and vasodilating agents (adenosine and prostacyclin). It is not necessary to elucidate the coordination of these functions and their relationship to the endothelial disorders in vascular diseases.

Actins↗
PubMedDate not supplied

Strial prostaglandins and leukotrienes. Biochemical characteristics and interrelationship with furosemide.

Synthesis of prostaglandins (PGs) was characterized in the lateral wall (LW) of guinea-pig cochlea. Basal synthesis at 37 degrees C was about 480 pg/LW (12.8 ng X mg-1 protein) for PGI2 and 85 pg/LW (2.3 ng X mg-1 protein) for PGE2, levelling out after 10 min of incubation. Incubation with arachidonic acid (10(-5) M) increased PGI2 and PGE2 synthesis by 44% and 1020%, respectively, showing that arachidonic acid availability is a synthesis-limiting factor. The stimulating effect of the Ca++ ionophore A23187 (5 X 10(-6) M) on PG synthesis was weak (about +50%) but was enhanced (about +140%) by preincubation with arachidonic acid. Angiotensin II (10(-6) M), vasopressin (5 X 10(-7) M), and furosemide (10(-8) to 10(-3) M) did not alter PG secretion. Neither aspirin nor indomethacin prevented the development of furosemide ototoxicity (endocochlear potential) in the rat. Perfusion with PGI2 influenced the furosemide effect in some instances.

Angiotensin II↗