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G Friedlander

Publications and source records attributed to G Friedlander.

32 records · Page 2Linked to original sources
PubMed1990

[Hyponatremia in the aged person].

Hyponatremia occurs frequently in the elderly. During aging, mechanisms which regulate the renal handling of water are modified, making easier the occurrence of hyponatremia: osmotic and non osmotic release of ADH is increased whereas renal diluting capacity is depressed. Hyponatremia occurs predominantly during administration of diuretic therapy and/or in congestive cardiac failure. In those circumstances, hyponatremia results from increased non osmotic release of ADH, changes in renal hemodynamics and excessive water intake, as compared to renal diluting capacity. Intracellular hyperhydratation may lead to neurologic damage resulting either from the disorder itself or from a too rapid correction. The latter may be complicated by a cerebral demyelination syndrome. This risk makes necessary to define rules for correction of hyponatremia.

Aged↗
PubMed1989

Protein kinase C activation has dissimilar effects on sodium-coupled uptakes in renal proximal tubular cells in primary culture.

Protein kinase C (Ca2+/phospholipid-dependent enzyme) was shown to be present in renal brush border membranes. To evaluate the influence of protein kinase C activation on three apical transport systems, we studied the effect of phorbol myristate acetate (PMA) and of two diacylglycerol analogs, oleoylacetylglycerol and dioctanoylglycerol, on sodium-dependent uptakes of phosphate (Pi), L-alanine, and alpha-methyl-D-glucopyranoside (MGP), as well as on specific phlorizin binding, in cultured rabbit proximal tubular cells. PMA, at 100 ng/ml, decreased the Vmax of Pi and MGP uptake by 30 and 17%, respectively, but not that of alanine uptake. None of the Km values were affected. PMA also decreased the number of phlorizin binding sites by 40%. PMA-induced inhibition of Pi and MGP uptake was time- and concentration-dependent, was mimicked by oleoylacetylglycerol, dioctanoylglycerol, and the diacylglycerol kinase inhibitor R59022, and was reversed by the protein kinase C antagonist 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7). The effects of PMA persisted in the presence of amiloride and dimethyl amiloride, and were potentiated by Ca2+ ionophore A23187. Opening of tight junctions blunted subsequent PMA-induced decrease of MGP uptake, but not of Pi uptake. It is concluded that: (i) activation of protein kinase C does not affect similarly Na-Pi, Na-hexose, and Na-alanine cotransport; and (ii) different pathways are likely to be involved in the observed effects.

Amino Acids↗
PubMed1989

Renal functional reserve.

Renal functional reserve represents the capacity of the kidney to increase its level of operation in response to certain demands. The reserve of glomerular filtration rate and of renal blood flow is discussed from the following points of view: evaluation, measurement, mechanisms involved and significance. Data from the literature are discussed which show (i) that the mechanism of the hyperfiltration seen in the early stage of diabetic nephropathy may be different from the hyperfiltration induced by infusion of amino acids, (ii) that the remaining kidney in healthy kidney donors maintains its functional reserve, and (iii) that the functional reserve is fairly well maintained as long as the glomerular filtration rate is decreased only moderately. The reserve of tubular functional capacity is discussed from the point of view of concentration and dilution and of acidification and alkalinization.

Blood Flow Velocity↗
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↗
PubMed1988

Tumor necrosis factor stimulates prostaglandin production and cyclic AMP levels in rat cultured mesangial cells.

Human recombinant tumor necrosis factor-alpha (TNF) was found to stimulate the production of prostaglandins (PG) by cultured rat mesangial cells. This effect was demonstrable from 6 h, was dose dependent and affected the synthesis of PGE2, PGF2 alpha, and 6-keto-PGF1 alpha. It required both RNA and protein synthesis but was not associated with a modification of cell proliferation. TNF also stimulated adenosine 3'-5' cyclic monophosphate (cAMP) levels in the mesangial cell culture medium. Indomethacin suppressed the effect of TNF on PGs but only reduced that on cAMP, indicating that PG production partly mediates the increase in cAMP. These findings demonstrate that mesangial cells can be a target for TNF and that the mechanism of TNF action includes stimulation of both PG production and cAMP levels.

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Increase in membrane fluidity and opening of tight junctions have similar effects on sodium-coupled uptakes in renal epithelial cells.

Apical membranes of renal epithelial cells were shown to be more rigid than other plasma membranes, due in part to the abundance of sphingomyelin among their constituent phospholipids. Tight junctions play a key role in maintaining differences between the apical and the basolateral domains of the plasma membrane with respect to their lipid composition and fluidity. To evaluate the influence of alterations of membrane fluidity on the activity of two apically located transport systems, we compared the effect of opening of tight junctions, by a preincubation period in calcium-deprived medium and of increasing fluidity, with benzyl alcohol, on Na-dependent uptakes of Pi and alpha-methyl-D-glucopyranoside (MGP) in intact, confluent LLC-PK1 cells and MDCK cells. Benzyl alcohol, at 10 mM, increased the Vmax of Pi uptake by 55 and 42% in LLC-PK1 cells and MDCK cells, respectively, but decreased the Vmax of MGP uptake in LLC -PK1 cells by 23%. Similarly to 10 mM benzyl alcohol, opening of tight junctions also increased the Vmax of Pi uptake by 45 and 46% in LLC-PK1 cells and MDCK cells, respectively, and depressed MGP uptake in LLC-PK1 cells by inducing a 15% decrease of the Vmax. None of the two maneuvers (i.e. addition of benzyl alcohol or opening of tight junctions) affected the Km values of the transport systems. From these results it is concluded that (i) the increase in membrane fluidity, achieved either by benzyl alcohol or by opening of tight junctions, affects Na-Pi and Na-glucose cotransports differently, reflecting differences in the lipid environments of the two transport systems, and (ii) membrane fluidity might play a physiological role in the modulation of the activity of transport systems.

Animals↗
PubMed1988

Asymmetry of plasma membrane lipid order in Madin-Darby Canine Kidney cells.

Fluorescence anisotropy experiments have been done to estimate, in situ, the lipid order of the plasma membrane of polarized Madin-Darby Canine Kidney cells (MDCK) grown on glass cover slips and labeled by 1-[4-(trimethylamino)phenyl]-6-phenylhexa-1,3,5-triene (TMA-DPH), a specific marker of the plasma membrane of living cells. Fluorescence microscopy, back-exchange, and quenching experiments indicated that TMA-DPH labeled the highly ordered (r greater than or equal to 0.32, 37 degrees C) apical domain of the plasma membrane of confluent monolayers. Opening of tight junctions or addition of the probe to cell suspensions resulted in a homogeneous distribution of TMA-DPH over the cell surface and in a marked decrease in anisotropy (0.27 less than or equal to r less than or equal to 0.29) that was due neither to a direct effect of Ca2+ on the probe nor to a change in fluorescence lifetime. Our data indicate that the apical domain, likely the external leaflet, of the plasma membrane of polarized MDCK cells is much more ordered than its basolateral counterpart.

Animals↗
PubMed1987

Benzyl alcohol increases membrane fluidity and modulates cyclic AMP synthesis in intact renal epithelial cells.

To evaluate a possible modulation by membrane fluidity of hormonal, cAMP-mediated effects on renal epithelial cells, we studied the effect of the neutral local anesthetic, benzyl alcohol, on membrane fluidity and on basal and stimulated intracellular cAMP content in intact MDCK cells. Benzyl alcohol induced a dose-dependent decrease of lipid order which was measured by steady-state fluorescence anisotropy using trimethylammonium-diphenylhexatriene and propionyl-diphenylhexatriene as fluorescent probes. Benzyl alcohol induced a 2-fold increase in basal cAMP content, likely as a consequence of increased prostaglandin synthesis since this effect was abolished by indomethacin. The effect of benzyl alcohol on stimulated cAMP synthesis depended on the nature of the ligand: 10 mM benzyl alcohol increased significantly the stimulatory effect of prostaglandin E2, glucagon and forskolin but not of vasopressin. At higher concentrations (40 mM), benzyl alcohol did not affect significantly the glucagon-stimulated cAMP content, while it inhibited significantly the prostaglandin E2-, forskolin- and vasopressin-stimulated cAMP synthesis. The 40 mM benzyl alcohol-induced inhibition was reversed by 1 mM Mn2+, which is known to block the inhibitory GTP-binding protein Ni. These results suggest that: (i) the various components of the adenylate cyclase-cAMP system and their coupling are affected differently by changes in membrane fluidity, which might reflect differences in their lipid environment, (ii) changes in membrane fluidity can modulate responses of renal tubular cells to hormones, and thus tubular functions.

Animals↗
PubMed1987

Protein kinase C activators and bradykinin selectively inhibit vasopressin-stimulated cAMP synthesis in MDCK cells.

To evaluate a possible modulation by protein kinase C of hormonal, cAMP-mediated effects on renal epithelial cells, we studied the effect of protein kinase C activators and of bradykinin on intracellular cAMP accumulation in MDCK cells. A 15-min pretreatment of cells with phorbol 12-myristate 13-acetate or 1-oleoyl-2-acetylglycerol induced a dose-dependent inhibition of vasopressin-stimulated cAMP synthesis, but not of basal or glucagon-, prostaglandin E2-, and forskolin-stimulated cAMP generation. 4 alpha-Phorbol 12,13-didecanoate, inactive on protein kinase C, did not affect cAMP accumulation. Bradykinin (0.1-10 microM) also inhibited the stimulatory effect of vasopressin on cAMP synthesis in a concentration-dependent manner, but affected neither basal cAMP content, nor its stimulation by glucagon, prostaglandin E2 and forskolin. The effect of activators of protein kinase C and of bradykinin occurred while renal prostaglandin synthesis was blocked with indomethacin. The inhibitory effect of protein kinase C activators and bradykinin on cAMP generation was reversed by the protein kinase C inhibitor H7, was enhanced by monensin, one effect of which is to block the recycling of membrane receptors, and persisted when the GTP-binding protein N1 was blocked with 1 mM Mn2+. Our data suggest that: protein kinase C can modulate the tubular effects of vasopressin by inhibiting cAMP generation; this effect is not mediated by renal prostaglandins, and might result from a direct action on the vasopressin receptor, or on its coupling with Ns; the modulation by bradykinin of vasopressin effects are likely to be exerted, at least partly, through activation of protein kinase C.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1987

Renal effects of platelet-activating factor in the rat.

The renal glomerular and tubular effects of the platelet-activating factor (Paf-acether) were studied, by clearance techniques, in acutely thyroparathyroidectomized Brattleboro rats infused with Paf-acether at the rate of 1.25, 2.5 or 5 ng/min/100 g bw. Paf-acether infusion was accompanied by decreases of urinary flow rate, calcium, and magnesium urinary excretion, whereas decreases of mean arterial pressure and glomerular filtration rate did not exceed 20% of control values for the highest perfusion rate of Paf-acether. These changes in tubular function were partially (calcium excretion) or totally (urinary flow rate and magnesium excretion) reversed after Paf-acether infusion was discontinued. Sodium and potassium excretion did not vary significantly during Paf-acether infusion, but increased dramatically after discontinuation of Paf-acether infusion. Infusion of lyso-Paf-acether or ethoxy-Paf-acether, two biologically less active structural analogues of Paf-acether, did not elicit any change in the variables studied. These data suggest that Paf-acether, when locally released by the kidney in pathological conditions, might affect both glomerular and tubular functions, possibly through different mechanisms.

Animals↗
PubMed1986

Somatostatin and alpha 2-adrenergic agonists selectively inhibit vasopressin-induced cyclic AMP accumulation in MDCK cells.

The effect of somatostatin and alpha 2-adrenergic agonists on cyclic AMP accumulation was examined in MDCK cells, grown in defined medium. These hormones inhibited vasopressin-induced cyclic AMP formation, without affecting either the basal or the glucagon- and prostaglandin E2-stimulated level. Pretreating the cells with pertussis toxin, or incubating them with MnCl2 at a low concentration reversed the effect of somatostatin and alpha 2-agonists. These results suggest that somatostatin and norepinephrine could selectively modulate the renal effect of vasopressin, via the inhibitory regulatory subunit (Ni) of adenylate cyclase.

Adenylate Cyclase Toxin↗
PubMed1985

Decreased calcium and magnesium urinary excretion during prostaglandin synthesis inhibition in the rat.

The effect of endogenous renal prostaglandins on calcium and magnesium reabsorption was investigated. Renal tubular handling of calcium and magnesium was studied by clearance methods in anesthetized Sprague-Dawley and Brattleboro rats, either intact or thyroparathyroidectomized (ATPTX), before and during prostaglandin synthesis inhibition by meclofenamate, indomethacin, or piroxicam infusion. These three inhibitors had similar effects on calcium and magnesium excretion: A significant decrease in absolute and fractional excretions of both cations was observed in intact Sprague-Dawley rats, and in ATPTX rats of both strains, but not in intact Brattleboro rats. These results suggest an inhibitory effect of prostaglandins on vasopressin-, glucagon-, but not PTH-mediated calcium and magnesium reabsorption. This effect is likely to occur in the thick ascending limb of Henle, which is both a target site for these polypeptidic hormones, and a segment where the bulk of calcium and magnesium is reabsorbed.

Animals↗
PubMed1977

[Activities of pulmonary phospholipases of fetal rats. Variations during development].

Turnover of adult rat lung phospholipids implies intervention of phospholipases. This work clearly demonstrates: There is in fetal or adult rat lung an inactive form of phospholipase that is convertible to an active form by the action of lysed platelets. An increase of both active and inactive forms of the fetal enzyme with gestational age. The fact that an important part of these activities, at the time of birth, are in the inactive form implies a control mechanism affecting levels of each form of lung phospholipases. These data are discussed in relation to the possible role of the lung phospholipases in Respiratory Distress Syndrome.

Aging↗