[Hyperhydration. Etiology, physiopathology, diagnosis, principles of treatment].
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Humans↗
Biomedical subjects
G Friedlander
Publications and source records attributed to G Friedlander.
[Renal functional reserve].
The term "renal functional reserve" (RFR) refers commonly to the reserve of glomerular filtration rate (GFR) and renal blood flow. RFR can be elicited by an oral protein load or by infusion of aminoacids, glucagon, or dopamine. The increase in GFR which follows aminoacid administration results from a cascade of events including at least pancreatic release of glucagon, involvement of an hepatic step yet unidentified, and renal synthesis of vasodilatory prostaglandins. RFR represents a constant fraction of baseline GRF as long as the latter is above 40-50 l/min. It has been suggested tha permanent challenge of RFR, which occurs in protein-rich diet or during the hyperfiltration phase of diabetic nephropathy, might lead to and accelerate impairment of renal function. The relevance of RFR measurement as a tool to predict the evolution of renal function in various types of renal diseases remains to be evaluated.
Female↗
Sphingomyelin and cholesterol modulate sodium coupled uptakes in proximal tubular cells.
Sphingomyelin (SM) and cholesterol are major lipid species of apical membranes in renal proximal tubular cells and confer to these membranes a low fluidity. Changes in membrane fluidity and/or lipidic composition were shown to affect the activity of cotransport systems of renal apical membranes. We evaluated the effect of decreasing membrane SM content on lipidic composition, membrane fluidity and sodium (Na)coupled uptakes in rabbit proximal tubular cells in primary culture. Sphingomyelinase (SMase) (30 to 250 mU/ml) decreased [3H]choline-labeled SM content, decreased cholesterol content, and increased cholesterol esterification. SMase did not modify membrane fluidity on isolated brush border membranes. SMase decreased Vmax of Na-dependent uptake of phosphate and alpha-methyl-D-glucoside, but not of alanine. SMase did not influence protein kinase C-induced inhibition of phosphate and glucose uptake. Increasing membrane cholesterol content with cholesterol-enriched liposomes subsequently to SMase action restored in part glucose uptake, but not phosphate uptake. In conclusion, SM degradation affected Na-phosphate and Na-glucose cotransports through changes in both SM and cholesterol contents of apical proximal membranes; these changes seemed to occur independently from changes in bulk membrane fluidity. These results suggest that SM and cholesterol have distinct and intricated roles in accessibility and/or activity of apical cotransport systems.
Animals↗
Membrane fluidity and transport properties in epithelia.
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Animals↗
Modulation of Na-H exchange activity by angiotensin II in opossum kidney cells.
Angiotensin II (ANG II) was shown to modulate transport in the renal proximal tubule through both inhibition of adenylate cyclase and protein kinase C (PKC) activation. We evaluated the effects of ANG II on adenosine 3',5'-cyclic monophosphate (cAMP) content and Na-H exchange activity (amiloride-sensitive Na influx) in two strains of opossum kidney (OK) cells originating from different sources, OK-VD and OK-RR cells. In OK-VD cells, ANG II inhibited basal and parathyroid hormone (PTH)-induced cAMP generation in a pertussis toxin-sensitive manner and reversed PTH inhibition of Na-H exchange. These effects of ANG II were prevented by PD 123319, a selective nonpeptide antagonist of AT2 receptors. In contrast, DuP 753, which antagonizes selectively AT1 receptors, had no effect. In OK-RR cells, ANG II had no effect on cAMP content and decreased Na-H exchange activity. The effect of ANG II persisted in the presence of PTH but was abolished by PKC downregulation and by DuP 753, but not by PD 123319. In conclusion, two types of ANG II receptors, coupled to distinct signaling pathways, were expressed independently in OK cells originating from two different sources and mediated opposite effects of ANG II on Na-H exchange activity. Those models provide a powerful tool for studying the intracellular steps involved in the tubular effects of ANG II and to evaluate the effect of pharmacological inhibitors of ANG II binding to its receptors.
Amiloride↗
Impairment of sodium-coupled uptakes by hydrogen peroxide in alveolar type II cells: protective effect of d-alpha-tocopherol.
Hydrogen peroxide (H2O2) is likely to play an important role in oxidant alveolar epithelium injury. We investigated the effect of H2O2 on uptake of phosphate, alanine in cultured rat alveolar type II cells. H2O2 induced inhibition of Na-dependent component of phosphate and alanine uptakes in time- and concentration-dependent manner. Twenty minutes exposure to 2.5 mM H2O2 decreased the maximum velocity (Vmax) of phosphate and alanine uptake by 50 and 62%, respectively, whereas Michaelis constant (Km) values were unchanged. H2O2 also decreased Na-K-ATPase activity, measured by ouabain-sensitive rubidium influx, and this effect was independent of H2O2-induced ATP depletion. A lipid-soluble antioxidant, d-alpha-tocopherol (20 microM, 24 h), prevented H2O2-induced decrease in Na-coupled uptake and Na-K-ATPase activity. These results indicate that H2O2 affects Na-dependent phosphate and alanine uptakes and suggest that this effect may be related at least, in part, to a decrease in Na transmembrane gradient, since H2O2 also affects Na-K-ATPase activity. The protective effect of d-alpha-tocopherol suggests that peroxidation of the membrane lipids is likely to be involved in the observed effects.
Adenosine Triphosphate↗
Ion transport by primary cultures of Mongolian gerbil middle ear epithelium.
The transport properties of Mongolian gerbil middle ear epithelial cells grown in primary culture were studied. These cells formed polarized monolayers that exhibited domes on nonporous supports. On porous supports, monolayers developed an apical-negative transepithelial electric potential difference (VT = -37.2 +/- 2.7 mV) and a transepithelial resistance (RT = 519 +/- 56 omega.cm2). The short-circuit current equivalent (Ieq) was 62.4 +/- 6.2 microA/cm2 (mean +/- SE, n = 15). Na+ and Cl- accumulated in the basal bath and generated a basolateral hyperosmolarity that drove a net water flow. Amiloride (10 microM), when added to the apical but not to the basal bath, induced a 23.4 +/- 1.5 mV and 44.1 +/- 1.3 microA/cm2 decrease of VT and Ieq, respectively, while RT increased by 403 +/- 69 omega.cm2 (P less than 0.001, n = 15). Exposure of the monolayers to a low-Cl- solution (30 mM) enhanced the transepithelial potential, possibly by means of a Cl- secretion through apical Cl- channels. Isoproterenol (10(-4) M basolateral) increased intracellular adenosine 3',5'-cyclic monophosphate (cAMP) content (concentration of half-maximal response = 2.5 x 10(-7) M) and decreased VT, RT, and Ieq. The isoproterenol-induced fall of VT occurred even in the presence of low-Cl-solutions. This suggested an increase of the paracellular pathway conductance, although there was no significant modification of the mannitol permeability.(ABSTRACT TRUNCATED AT 250 WORDS)
Amiloride↗
Mechanisms whereby extracellular adenosine 3',5'-monophosphate inhibits phosphate transport in cultured opossum kidney cells and in rat kidney. Physiological implication.
The mechanism of phosphaturia induced by cAMP infusion and the physiological role of extracellular cAMP in modulation of renal phosphate transport were examined. In cultured opossum kidney cells, extracellular cAMP (10-1,000 microM) inhibited Na-dependent phosphate uptake in a time- and concentration-dependent manner. The effect of cAMP was reproduced by ATP, AMP, and adenosine, and was blunted by phosphodiesterase inhibitors or by dipyridamole which inhibits adenosine uptake. [3H]cAMP was degraded extracellularly into AMP and adenosine, and radioactivity accumulated in the cells as labeled adenosine and, subsequently, as adenine nucleotides including cAMP. Radioactivity accumulation was decreased by dipyridamole and by inhibitors of phosphodiesterases and ecto-5'-nucleotidase, assessing the existence of stepwise hydrolysis of extracellular cAMP and intracellular processing of taken up adenosine. In vivo, dipyridamole abolished the phosphaturia induced by exogenous cAMP infusion in acutely parathyroidectomized (APTX) rats, decreased phosphate excretion in intact rats, and blunted phosphaturia induced by PTH infusion in APTX rats. These results indicate that luminal degradation of cAMP into adenosine, followed by cellular uptake of the nucleoside by tubular cells, is a key event which accounts for the phosphaturic effect of exogenous cAMP and for the part of the phosphaturic effect of PTH which is mediated by cAMP added to the tubular lumen under the influence of the hormone.
Adenosine↗
Antidiuretic hormone stimulation of adenylate cyclase in semicircular canal epithelium.
Basal adenosine 3',5'-cyclic monophosphate (cAMP) content and the modulation of its production were studied in the frog's semicircular canal epithelium. This epithelium secretes endolymph, a K(+)-rich, positively polarized fluid. The basal cAMP content measured by microradioimmunoassay was 244 +/- 14.2 fmol/structure per 5 min (n = 30). This content was increased about 8 times by 10(-5) M forskolin. Vasotocin, the frog antidiuretic hormone, increased the cAMP production by factors of 1.3 and 3.3 at concentrations of 10(-8) M and 10(-7) M, respectively. This stimulatory effect of vasotocin was blunted by the addition of alpha 2-adrenergic agonists, such as 10(-8) M-10(-5) M norepinephrine, in the presence of 10(-5) M propranolol, or 10(-5) M clonidine. Prostaglandin E2 at a concentration of 10(-8) M, which did not affect the cAMP production, did not modify the response to vasotocin. Glucagon (10(-6) M), calcitonin (10(-6) M), and parathyroid hormone (10 units/ml) did not affect the cAMP content. Prostaglandin E2 (10(-7) M) and the beta-adrenergic agonist isoproterenol (10(-6) M) stimulated the cAMP production by a factor of 1.6. These results indicate that the frog semicircular canal is a target of both vasotocin and catecholamines and that catecholamines through alpha 2-receptors modulate vasotocin-induced cAMP generation. Further, this interaction might be of physiological relevance in the modulation of ion transport in this structure.
Adenylyl Cyclases↗
Protein kinase C modulates cAMP content in proximal tubular cells: role of phosphodiesterase inhibition.
The present study was designed to evaluate whether protein kinase C (PKC) activation affects hormone-modulated adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in rabbit renal proximal tubular cells in primary culture. When intracellular cAMP content was measured in the presence of Ro 20-1724, a selective inhibitor of type III phosphodiesterase (PDE), activation of PKC by the phorbol ester phorbol 12-myristate 13-acetate (PMA) or by diacylglycerol kinase inhibitor R 59022 reinforced parathyroid hormone (PTH)- and forskolin-stimulated cAMP accumulation. During PKC activation, the inhibitory effect of norepinephrine on cAMP content persisted, whereas that of angiotensin II (ANG II) was blunted. In contrast, PKC activators had no effect on cAMP content during PDE blockade by the nonspecific inhibitor 3-isobutyl-1-methylxanthine (IBMX). These data suggested that PKC might affect cAMP degradation through inactivation of a Ro 20-1724-insensitive PDE. The possibility that the involved PDE was calcium sensitive was assessed; during PDE inhibition by Ro 20-1724, but not by IBMX, calcium ionophore A23187 inhibited PTH-stimulated cAMP accumulation and PMA abolished the effect of A23187. Finally, neither PKC inhibition by staurosporine nor its downregulation modified the magnitude of PTH-induced cAMP accumulation. In conclusion, 1) in proximal tubular cells PKC affects cAMP degradation rather than synthesis, possibly via inactivation of a calcium-sensitive PDE; 2) PKC modulates PTH-ANG II interaction; and 3) this pathway is likely to play a role in the fine tuning of the effect of PTH and ANG II in the proximal tubule.
Angiotensin II↗
Adenylate cyclase in the semicircular canal. Hormonal stimulation and ultrastructural localization.
The modulation of the cyclic AMP (cAMP) production and the cytochemical localization of adenylate cyclase were studied in isolated semicircular canal epithelium of the frog. The basal cAMP content, as measured by radioimmunoassay, was 344 +/- 37.8 fmoles/structure/5 min (mean +/- SEM, n = 41). This content was increased 6- to 8-fold by forskolin (10(-7) M to 10(-5) M). Among the tested drugs, only prostaglandin E2, isoproterenol, and vasotocin increased the cAMP production: 1.7-fold by prostaglandin E2 (1.5 X 10(-7) M) and isoproterenol (10(-6) M), and 1.3- and 3.3-fold by vasotocin at 10(-8) M and 10(-7) M, respectively. The addition of alpha 2-adrenergic agonists blunted the stimulatory effect of vasotocin. The adenylate cyclase was evidenced in both the basolateral and apical membranes of the dark cells. Vasotocin stimulated only the apical adenylate cyclase of dark cells. These results indicated that the adenylate cyclase located in the apical dark cells of the semicircular canal was stimulated by the antidiuretic hormone which may be involved in the regulation of the endolymph secretion.
Adenylyl Cyclases↗
[Culture of the epithelium of middle ear in the study of seromucous otitis].
Preliminary results on transport properties of middle ear epithelium in primary culture are reported. Primary cultures of Mongolian gerbil (Meriones unguiculatus) middle ear epithelial cells were undergone. These cells formed polarized monolayers that exhibited domes when grown to confluence on non porous support. Domes are the consequence of active transepithelial transports of solutes and water. On porous support, Na+ and Cl- accumulated in the basal bath and generated a basolateral hyperosmolarity that drove a net water flow. This solutes and water absorption was the consequence of an active Na+ transcellular transport, by means of apical sodium channels, that was responsible for the transepithelial potential difference, lumen negative: -39 +/- 1.2 mV (mean +/- SEM, n = 63). Transport of fluid and ions in the middle ear cavities could play a major role in keeping the cavities fluid-free and air-filled and modulating the mucociliary clearance. Modulation of these transports could be involved at the start of otitis media with effusion, and would contribute to the mucociliary clearance impairment.
Absorption↗
[The functional renal reserve].
The term "renal functional reserve" (RFR) refers commonly to the reserve of glomerular filtration rate (GFR) and renal blood flow. RFR can be elicited by an oral protein load or by infusion of amino acids, glucagon, or dopamine. The increase in GFR which follows amino acid administration results from a cascade of events including pancreatic release of glucagon, involvement of an hepatic step, and renal synthesis of vasodilatory prostaglandins. RFR represents a constant fraction of baseline GFR as long as the latter is above 40-50 ml/min. RFR becomes virtual for lower values of GFR. It has been suggested that permanent challenge of RFR, which occurs in protein-rich diet or during the hyperfiltration phase of diabetic nephropathy, might lead to and accelerate impairment of renal function. The relevance of RFR measurement as a tool to predict the evolution of renal function in various types of renal diseases remains to be evaluated.
Amino Acids↗
Increase in membrane fluidity modulates sodium-coupled uptakes and cyclic AMP synthesis by renal proximal tubular cells in primary culture.
In order to evaluate the influence of membrane fluidization on three apical transport systems and on a basolateral enzyme, and to analyse the mechanisms involved, we studied, in cultured rabbit proximal tubular cells, the effect of increasing concentrations of the local anesthetic drug benzyl alcohol on Na(+)-dependent uptakes of phosphate (Pi), methyl alpha-D-glucopyranoside (MGP), and L-alanine, as well as on basal and stimulated cyclic AMP content. At 10 mM, benzyl alcohol increased the Vmax of Pi uptake by 31%, decreased that of MGP uptake by 24%, and did not affect alanine uptake. Km values were not affected. Benzyl alcohol, up to 40 mM, increased in a concentration-dependent manner basal, PTH-stimulated, and cholera toxin-stimulated, but not forskolin-stimulated cyclic AMP accumulation. In the presence of 40 mM benzyl alcohol, the magnitude of PTH-induced inhibition of Pi uptake was enhanced from 11% to 24%. It is concluded that: (i) fluidization of apical membranes affected differently Na+/Pi, Na+/MGP, and Na+/alanine cotransports, reflecting differences in the lipidic environments of these transport system; (ii) fluidization of basolateral membranes enhanced PTH-stimulated cyclic AMP generation through improved coupling between the receptor-GS complex and the catalytic subunit of adenylate cyclase; (iii) these variations may result in physiological and pathophysiological modulation of the renal handling of solutes and of the phosphaturic effect of PTH.
1-Methyl-3-isobutylxanthine↗
Glucagon secretion is essential for aminoacid-induced hyperfiltration in man.
The role of glucagon as a mediator of aminoacid-induced alteration of renal haemodynamics was evaluated in man in three different protocols. In the first it was shown that the increase in glomerular filtration rate (GFR) and renal plasma flow (RPF) observed during an aminoacid infusion was prevented by the additional infusion of somatostatin (SRIF), but reproduced by a glucagon infusion in the presence of SRIF. In the second protocol it was shown that, at variance with normal subjects, six totally pancreatectomised patients, thus deprived of pancreatic glucagon secretion, did not increase their GFR and RPF when infused with amino-acids, whereas they exhibited the expected hyperfiltration when infused with glucagon. In the third protocol it was shown that glucagon infusion in a renal artery did not alter the homolateral renal haemodynamics. It is concluded that glucagon secretion is a mandatory step in the cascade of events linking the infusion of aminoacids to the renal hyperfiltration. Other steps beyond glucagon secretion are necessarily involved because glucagon has no direct renal effect.
Adult↗
Renal functional reserve.
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Angiotensin II↗
ADH modulates plasma membrane lipid order of living MDCK cells via a cAMP-dependent process.
Using 1-[4-(trimethylamino)phenyl]-6-phenyl-hexa-1,3,5-triene, a fluorescent probe that specifically labels the external leaflet of the plasma membrane of living cells, we examined the effects of antidiuretic hormone (ADH) and various agents known to raise intracellular adenosine 3',5'-cyclic monophosphate (cAMP) on the physical state of the plasma membrane of Madin-Darby canine kidney (MDCK) cells. In polarized cells grown as a monolayer, [desamino-Cys1, DArg8]-vasopressin (V2-agonist) elicited a biphasic decrease in the lipid order as estimated from the decrease in fluorescence anisotropy (from r = 0.317 to r = 0.304, 37 degrees C) of the apical domain of the plasma membrane, equivalent at the peak response (t = 5 min) to that produced by an upward shift in temperature of 5-6 degrees C. A similar response was obtained by adding dibutyryl cAMP to the monolayers. Experiments on cell suspensions further indicated that the biphasic decrease in lipid order could also be evoked by forskolin, prostaglandin E2, and bradykinin but not by bradykinin plus indomethacin and was inhibitable by the protein kinases inhibitor compound H7. These data demonstrate that the lipid order of the plasma membrane of MDCK cells can be modulated in situ by cAMP-dependent processes probably involving protein kinase A activity, i.e., that membrane "fluidity" might act in the regulation of the cellular function of living epithelial cells. They provide a rationale for the changes in lipophilic solute permeability that accompany the increase in water permeability of target cells on ADH administration.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
12-HETE modulates Na-coupled uptakes in proximal tubular cells: role of diacylglycerol kinase inhibition.
Inhibition of diacylglycerol (DAG) kinase, an alternative way to increase the cellular DAG level, was shown to reproduce, in renal proximal tubular cells, the inhibitory effect of protein kinase C (PKC) activators on Na-Pi and Na-alpha-methyl-D-glucopyranoside (MGP) cotransport. To evaluate whether 12S-hydroxyeicosatetraenoic acid (12S-HETE) or 12R-HETE, a DAG kinase inhibitor in endothelial cells, has a similar effect in proximal tubular cells, we studied the influence of this lipoxygenase product on Na-dependent uptake of Pi, MGP, and alanine, as well as on [14C]arachidonate-DAG content and [32P]phosphatidic acid (PA) content in rabbit proximal tubular cells grown as a primary culture. 12-HETE (1-10 microM) decreased [32P]PA content and stimulated [14C]DAG accumulation in a concentration-dependent manner. The labeled phosphatidylcholine, lysophosphatidylcholine, and sphingomyelin contents were not modified. 12-HETE also decreased DAG kinase activity of cell membranes. 12-HETE (10 microM) decreased the maximum velocity of Pi uptake by 36% and that of MGP uptake by 44% but did not affect alanine uptake. The effect of 12-HETE on transport was potentiated by calcium ionophore A23187 and was blunted by PKC downregulation. The effects of 12-HETE on lipid composition and transport were mimicked by R 59022, a pharmacological DAG kinase inhibitor. Neither arachidonic acid nor prostaglandin E2 reproduced the effects of 12-HETE. We conclude that in the proximal tubule, 12-HETE affected Na-dependent Pi and MGP cotransport through stimulation of PKC and that 12-HETE-induced activation of PKC is mediated by the inhibition of DAG kinase.
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗