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J Noël

Publications and source records attributed to J Noël.

13 recordsLinked to original sources
PubMed1992

Substrate-induced modulation of ATP turnover in dog and rabbit proximal tubules.

In dog proximal tubules in suspension, the addition of glucose increased significantly the ouabain-sensitive fraction of respiration, a response suppressed by phlorizin. The addition of alpha-methyl-D-glucoside (alpha-MG) had a modest effect and 3-O-methyl-D-glucoside (3-O-MG) had no effect. The different stimulation of the Na+,K(+)-ATPase activity elicited for each hexose could be explained by a different increment of net transepithelial flux of sodium induced by the sodium: hexose cotransport. This flux is a direct function of the transport characteristics of both luminal and antiluminal membranes of proximal cells for these sugars: glucose is rapidly transported by both membranes (allowing a large transepithelial flux of glucose: sodium) while alpha-MG is poorly transported by the basolateral, and 3-O-MG by the luminal, membrane of the dog proximal tubule (allowing a small transepithelial flux of hexoses and sodium). However the overall tubular respiration of dog proximal tubules was not increased by glucose addition because the increment in the ouabain-sensitive fraction was accompanied by a reciprocal decrement in an ouabain-insensitive but oligomycin- or N',N' dicyclohexylcarbodiimide (DCCD)-sensitive (or in the bafilomycin-sensitive) component of respiration. This component reflects the activity of a large BBM-bound H(+)-ATPase found in this species. The intracellular pH of dog proximal tubules in suspension was measured using the proton-sensitive fluorescent probe 2',7'-bis-2-(carboxyethyl)-5, (and 6)-carboxyfluorescein. Glucose application significantly alkalinized the cells. In contrast, other substrates such as lactate or acetate simultaneously acidified the cells and increased the ouabain-insensitive phosphorylative respiration of dog tubules. These observations suggest that a modulation of the activities of both the sodium and most probably the proton pump is elicited by substrate availability in suspensions of proximal tubules.

Adenosine Triphosphate↗
PubMed1991

Effects of isoflurane, halothane, and enflurane on myocardial flow and energy stores in the perfused rat heart.

The effect of three volatile anesthetics (halothane, enflurane, and isoflurane) on coronary flow and metabolic state of isolated rat hearts was studied. These anesthetics are coronary dilators and their effects are dose dependent. At 2 MAC (minimum alveolar concentration), isoflurane, enflurane, and halothane increase coronary flow by 114 +/- 5.9, 93 +/- 6.1, and 77 +/- 6.4%, respectively (p less than 0.001). At these concentrations, they also have a modest but significant metabolic effect causing a 30% reduction in myocardial ATP and phosphocreatine levels, with no significant modification in ADP and AMP concentrations. Energy charge and lactate/pyruvate ratio were also unaffected by these anesthetics. The vascular and metabolic effects were reversible within 2 and 30 min, respectively. Perfusion of the hearts with a Krebs-Henseleit solution without Pi did not interfere with the vascular and the metabolic effect of the anesthetics; however, in this case, ATP and phosphocreatine concentration did not return to control levels after their discontinuation despite full recovery of the vascular effect. These data suggest that the volatile anesthetics have direct coronary vascular and myocardial metabolic effects and that these effects occur independently.

Adenosine Diphosphate↗
PubMed1991

Basolateral glucose transport in distal segments of the dog nephron.

The transport of glucose by canine thick ascending limbs (TAL) and inner medullary collecting ducts (IMCD) was studied using tubule suspensions and membrane vesicles. The uptake of D-[14C(U)]glucose by a suspension of intact TAL tubules was reduced largely by phloretin (Pt), moderately by phlorizin (Pz), and completely suppressed by a combination of both agents. A selective effect of Pz on the transport of [14C]alpha-methyl-D-glucoside, but not on 2-[3H]deoxyglucose, was also observed in TAL tubules. In contrast, glucose transport was unaffected by Pz but entirely suppressed by Pt alone in IMCD tubules. The metabolism of glucose was largely suppressed by Pt but unaffected by Pz in both types of tubules. Membrane vesicles were prepared from the red medulla and the white papilla or from TAL and IMCD tubules isolated from these tissues. Vesicle preparations from both tissues demonstrated a predominant carrier-mediated, sodium-independent, Pt- and cytochalasin B-sensitive glucose transport. Following purification of basolateral membrane on a Percoll gradient, the sodium-insensitive D-[14C(U)]glucose transport activity copurified with the activity of the basolateral marker Na(+)-K+ ATPase in both tissues. However, a small sodium-dependent and Pz-sensitive component of glucose transport was found in membrane vesicles prepared from the red medulla or from thick ascending limb tubules but not from the papilla nor collecting duct tubules. The kinetic analysis of the major sodium-independent processes showed that the affinity of the transporter for glucose was greater in collecting ducts (Km = 2.3 mM) than in thick ascending limbs (Km = 4.9 mM). We conclude that glucose gains access into the cells largely through a basolateral facilitated diffusion process in both segments. However a small sodium-glucose cotransport is also detected in membranes of TAL tubules. The transport of glucose presents an axial differentiation in the affinity of glucose transporters in the renal medulla, ensuring an adequate supply of glucose to the glycolytic inner medullary structures.

Aerobiosis↗
PubMed1991

Metabolism of lactate by a suspension of dog thick ascending limbs: relations with transport.

The addition of substrate in the form of lactate (L), but not glucose (G), increases the respiration of canine thick ascending limb (TAL) segments in a saturable (above 2 mM) fashion. More than 60% of this stimulation is ouabain-sensitive (1 mM ouabain) even if L and G transport are both sodium-insensitive processes in TAL. Thus L, but not G, specifically stimulates Na+ entry in TAL cells and its subsequent transport by the Na+,K(+)-ATPase. If chloride is substituted for by gluconate, no significant substrate-induced stimulation of ouabain-sensitive respiration is observed. SITS (4-acetamino-4'-isothiocyanostilbene-2,2'-disulfonic acid) also interferes with the L-induced stimulation of respiration. Thus L entry in TAL appears to be directly or indirectly coupled to the transepithelial flux of Cl-. Furosemide (F), but not amiloride, also inhibits this stimulation suggesting that the accelerated Na+ entry triggered by the application of L occurs through the F-sensitive carrier or that lactate transport is F-sensitive in TAL cells. In accord, F specifically impairs the metabolism of L (as compared to G). These data suggest that in intact TAL tubules both lactate uptake and oxidation are directly or indirectly influenced by the transcellular flux of NaCl. This organization may participate to maintain a stoichiometry between the transport of NaCl and the availability of L to support the energetic needs of TAL cells.

Animals↗
PubMed1990

Relationship between intracellular ATP and the sodium pump activity in dog renal tubules.

To examine the potential effect of the cellular ATP concentration and of the phosphate potential on the function of the sodium pump in intact renal cells, the ATP content of dog cortical tubules was first modified by a 30-min preincubation with one of the following effectors: 5 or 10 mM fructose, 2.5 mM adenosine 5'-monophosphate (AMP), or 2.5 mM adenosine in the presence of substrates (10 mM glutamine + 1 mM glutamate with either 10 mM lactate (low ATP) or 10 mM pyruvate (high ATP)). The tubules were then incubated in Krebs-Henseleit saline using two different phosphate concentrations and the same substrate mixture. The ATP content in tubular cells was modified by these treatments, ranging from 2.2 to 5.7 mM. The oxygen uptake by the tubules was measured before and after application of a small amount of nystatin (0.05 mM, 6 mumol/g wet wt.), added to impose an identical and submaximal increment of work to the Na(+)-K+ ATPase in tubules, irrespective of their ATP condition. This manoeuvre was followed by the addition of 1 mM ouabain to inhibit the sodium pump and quantify the respiration related to the activity of the Na+ pump. No significant effect of the ATP content on the respiratory cost of the Na(+)-K+ ATPase activity was noted when the [ATP] was above the normal concentration of approximately 3.0 mM before or after introduction of nystatin. In a second group of experiments, tubules were treated with 0.1 mM digitonin (13 mumol/g wet wt.) and resuspended in intracellular-like and sodium-free medium. The respiration was measured before and after the addition of increasing Mg-ATP concentrations (0-12 mM). A fixed quantity of Na+ (20 mM) was then introduced before ouabain was applied. The oxygen uptake was measured in these three conditions. We observed a fixed increment of ouabain-sensitive respiration upon stimulation of the pump activity by sodium at ATP concentrations ranging from 2 to 7 mM. The same observation applied when the free energy released from ATP hydrolysis ranged from -50 to -56 kJ.mol-1 and when the [ATP]/[ADP].[Pi] ratio ranged from 1.5 to 7.5 mM-1. These results suggest that the Na+:ATP stoichiometry of the Na(+)-K+ ATPase is not modified by [ATP] in dog cortical tubules when the ATP content is at or above the physiological value. Furthermore, the stoichiometry of the pump does not appear to change when the phosphate potential and (or) the free energy released from ATP hydrolysis are altered.

Adenosine Triphosphate↗
PubMed1990

Basolateral transport of lactate in dog thick ascending limbs.

Basolateral membrane vesicles (BLMV) isolated from both red outer medulla or from thick ascending limb segments isolated from the dog kidney were used to examine the process of lactate transport in this nephron segment. The BLMV preparation was enriched in Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) that represented 96% of the total ATPase activity of this preparation and the vesicles were largely under the right side-out orientation. On application of a OH- or HCO3- gradient (inside greater than outside), a secondary active lactate accumulation was observed, with characteristic transient overshoot. This phenomenon was shown to occur irrespective of the presence or absence of Na+, K+, or Cl-. The pH, but not the bicarbonate-driven, overshoot was abolished by nigericin (in presence of K+). Studies with valinomycin and K+ demonstrated that the generation of a membrane potential was not responsible for the acceleration of lactate transport, even if the amplitude of lactate accumulation was reduced in the presence of a bicarbonate gradient and valinomycin. A significant trans-stimulation of [14C]lactate transport by cold lactate was observed (under voltage-clamp condition). The transport was 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid insensitive but sensitive to furosemide (IC50 = 0.1 mM) and alpha-hydroxycyanocinnamate (IC50 = 1 mM). The kinetic parameters of the transporter revealed a single carrier with an apparent Michaelis constant of 1.7 mM and an apparent Vmax of 9.7 nmol.mg protein-1.30 s-1. The transporter was shown to be distinct from that of proximal tubule brush-border membrane or mitochondria (pyruvate). Thus thick ascending limbs possess a carrier-mediated lactate transport that can be used for lactate uptake (aerobic condition) or for lactate release (anaerobic glycolysis) according to metabolic processes imposed by the local oxygenation condition.

Animals↗
PubMed1989

Enzymatic basis of renal adaptation to acidosis in the dog.

The effect of pH on the activities of various enzymes along the ammoniagenic pathway was tested on dog kidney cortex homogenates in an attempt to identify the metabolic steps that could be directly influenced by a low pH in this species. The activity of alphaketoglutarate dehydrogenase was markedly stimulated by acidification of the medium that decreased abruptly the km for alphaketoglutarate. By contrast, succinyl CoA synthetase and malate dehydrogenase remained relatively insensitive to pH changes. The apparent km of malic enzyme for malate was markedly decreased by an acid medium. Therefore these findings suggest that an acid pH regulates the ammoniagenic pathway at two critical sites: alphaketoglutarate dehydrogenase and malic enzyme. These stimulated enzymatic activities may account for the changes in renal cortical concentrations of metabolites observed during metabolic or respiratory acidosis.

Acidosis↗
PubMed1989

Recurrent postoperative sciatica: evaluation with MR imaging and enhanced CT.

Magnetic resonance (MR) imaging and computed tomography enhanced with intravenous iodine injection (ECT) were prospectively compared in 80 patients in the diagnosis of recurrent postoperative sciatica. Diagnostic accuracy was determined with surgical verification. Isolated fibrosis was considered a contraindication to surgery. A decision to operate was made in 56 of the 80 patients on the basis of MR imaging findings; in 21 of the 56, the decision was also made on the basis of ECT findings. Of the 80 patients, 45 underwent surgery, In all but one of these patients, the diagnosis made on the basis of MR imaging findings was confirmed with surgical analysis. The only surgical finding that did not agree with MR imaging findings was a calcification of the common posterior ligament. The 21 diagnoses of disk herniation based on ECT findings were confirmed surgically, but among the 24 diagnoses of fibrosis made with the help of ECT, there were actually 19 recurrent herniations, four herniations with fibrosis, and one herniation at the level above the previously resected disk. MR imaging seems to be the investigation of choice in diagnosing the cause of recurrent postoperative sciatica.

Adult↗
PubMed1989

Metabolic effects of acetate on the heart.

The effects of various substrates (15 mM glucose, 5 mM glucose, 20 mM acetate, or a combination of these substrates) on the coronary blood flow and on the energetic status of myocytes were studied in isolated perfused rat hearts. We demonstrate that low level glucose (5 mM) or high concentration of acetate (20 mM) leads to a simultaneous fall in tissue ATP, rise in tissue adenosine, and significant increment in coronary blood flow. The latter effect is especially marked with 20 mM acetate. Dipyridamole (10(-6) M) does not enhance the vasodilatation induced by acetate. The provision of 15 mM glucose together with 20 mM acetate fully prevents these changes, indicating that the vasodilatation induced by acetate is probably mediated by metabolic changes. The evidence supports the concept that a redistribution of blood flow together with a fall in tissue ATP may explain some of the adverse effects of acetate dialysis in man, and suggests that the provision of glucose may alleviate these changes.

Acetates↗
PubMed1985

Isoproterenol induces a ribosomal modification in the heart and the skeletal muscle of hamsters.

The protein synthesis activity of heart, skeletal muscle and liver polysomes from isoprotenerol-treated and control hamsters has been compared in an in vitro non-initiating translation system. Heart and skeletal muscle polysomes from treated hamsters were less active than controls and required a higher magnesium concentration for optimal protein synthesis. These results suggest that there is a conformational modification in heart and skeletal muscle ribosomes from isoprotenerol-treated hamsters. No such change was observed with ribosomes from the liver of isoproterenol-treated hamsters.

Animals↗
PubMedDate not supplied

Fluorescence measurement of intracellular pH on proximal tubule suspensions. The need for a BCECF sink.

BCECF is used for intracellular pH (pHi) measurement in microperfused tubules. In this case, the perfusate washes out all BCECF leaking from the cells away from the optical light path. We have explored the use of BCECF for pHi determination on suspensions of dog renal proximal tubules (Percoll). This raises specific problems due to the accumulation of BCECF in the extracellular compartment generated by desesterification of BCECF-AM during loading and to leaking of BCECF into the extracellular medium occurring during the waiting time and during the measurement procedure. Repeated washing of the suspension reduced in part this contamination but did not eliminate the continuous leakage of BCECF: the specific intracellular signal is progressively reduced. We have examined the use of anion exchange resin (Dowex 1X-8, 200-400 mesh, Cl- form) to bind the extracellular BCECF (negatively charged). Dowex beads glued to one wall of the cuvette out of the optical path constitute an optically neutral sink removing BCECF as it leaks out of the cells. Using this technique, we had estimated the pHi of dog proximal tubule to 7.374 +/- 0.032 at extracellular pH of 7.325 +/- 0.021. The cellular pH is acutely, but transiently, alkalinized by NH4Cl and acidified by Na acetate. The BCECF signal was calibrated using nigericin. This technique improves significantly the measurement of pHi by BCECF fluorescence in tissue suspensions.

Animals↗