Albumin Transport

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Alain Tedgui - One of the best experts on this subject based on the ideXlab platform.

  • Albumin Transport characteristics of rat aorta in early phase of hypertension
    Circulation Research, 1992
    Co-Authors: Alain Tedgui, Regine Merval, Bruno Esposito
    Abstract:

    The effects of early-stage hypertension on the macromolecular Transport characteristics of the aorta have been investigated in rats 1 week after the ligature of the abdominal aorta between the two renal arteries. The animals were left untreated or treated for 1 week with an angiotensin converting enzyme inhibitor (enalapril, 6 mg/kg per day). Blood pressure of a subgroup of hypertensive rats was acutely lowered to a normal level by injection of enalaprilat (1.5 mg/kg) at the time of the experiment. 131I-Albumin and 125I-Albumin were injected 90 minutes and 5 minutes, respectively, before the rats were killed. The transmural distribution of the relative tissue concentrations across the wall was obtained using a serial frozen-section technique. Short-term Albumin uptake permitted calculation of apparent endothelial permeability coefficients, and 90-minute uptake was used to estimate the steady-state Albumin distribution within the media. The effect of early-stage hypertension on the characteristics of the arterial macromolecular Transport depended on the aortic site; the ascending aortic arch appeared not to be affected. In the thoracic and abdominal aorta, the endothelial permeability coefficients increased significantly in hypertensive rats. This increase was not a direct effect of the arterial pressure, since the values were not significantly different when the pressure was acutely normalized. The 90-minute Albumin concentration in the media was enhanced in hypertensive rats and returned to the normal value by acutely lowering the blood pressure, indicating that the increase observed in hypertensive rats resulted from a direct effect of pressure, possibly increased pressure-driven convection and/or pressure-induced stretching of the wall. Treatment by angiotensin converting enzyme inhibitor prevented hypertension and protected against its effects in hypertensive animals.

  • Effect of the Transmural Pressure on LDL and Albumin Transport and Distribution Across the Intact Arterial Wall
    Biofluid Mechanics, 1990
    Co-Authors: Patrick A. Curmi, L Juan, Alain Tedgui
    Abstract:

    Recent progress in biology of the arterial wall have given a framework to account for the formation of atherosclerotic lesions. In particular, foam cells appear to be the result of low density lipoprotein (LDL) oxidation and of its uptake by the scavenger receptor of monocytes-macrophages that have migrated into the intima [1]. However, early plasma LDL accumulation in the subendothelial space seems to be required to trigger this process. In this respect, Transport of macromolecules may play a major role in atherogenesis. As with most of the plasma macromolecules, LDL pass through the vascular endothelium and are then Transported by diffusion/convection across the media [2].

  • effect of transmural pressure on low density lipoprotein and Albumin Transport and distribution across the intact arterial wall
    Circulation Research, 1990
    Co-Authors: Patrick A. Curmi, L Juan, Alain Tedgui
    Abstract:

    To investigate the effect of hyperpressure on the Transport of low density lipoprotein (LDL) and Albumin in the arterial wall, we measured in vitro the uptake of both iodine-131-labeled LDL and iodine-125-labeled Albumin in intact rabbit thoracic aorta, held at in vivo length and pressurized to 70 or 160 mm Hg. Arteries were incubated for 2 hours (n = 8) at 70 mm Hg, and for 5 minutes (n = 4), 30 minutes (n = 4), 1 hour (n = 5), and 2 hours (n = 5) at 160 mm Hg. The transmural distribution of the relative concentrations of LDL (CLDL) and Albumin (Calb) across the wall was determined by using a serial frozen sectioning technique. At 70 mm Hg, the mean medial CLDL and Calb values were 0.0018 +/- 0.0007 and 0.0039 +/- 0.0013, respectively. At 160 mm Hg, CLDL and Calb were markedly increased. The distribution of labeled Albumin was almost uniform across the media and reached a steady state after 30 minutes, whereas labeled LDL accumulated in the first inner layers, a steady state being achieved after 1 hour. The 1-hour values of CLDL in the first and second luminal sections (0.24 +/- 0.03 and 0.13 +/- 0.05, respectively) were much higher than those of Calb, the CLDL/Calb ratios being 4.12 +/- 0.94 and 2.34 +/- 0.42 (p less than 0.01), respectively. In the subsequent sections, the CLDL decreased markedly and became much lower than the Calb, the CLDL/Calb ratio averaging 0.2 in the two-thirds outer media. To investigate whether LDL was trapped at high pressure in the inner layers, vessels were exposed to a tracer-free intraluminal solution for 30 minutes, after a 30-minute incubation with tracers. After washout, Albumin was almost totally removed from the wall, while the CLDL were practically unchanged. Compaction of the media induced by high distending stresses applied to the vessel might have hindered the efflux of LDL, whereas Albumin moved freely through the wall. Synergy between increased endothelial permeability and compaction of the media together with enhanced pressure-driven convection might account for the marked increase in LDL concentration observed in the inner wall at high pressure.

A B Malik - One of the best experts on this subject based on the ideXlab platform.

  • Role of Src-induced dynamin-2 phosphorylation in caveolae-mediated endocytosis in endothelial cells.
    Journal of Biological Chemistry, 2004
    Co-Authors: Ayesha N. Shajahan, C Tiruppathi, A B Malik, Barbara Timblin, Raudel Sandoval, Richard D. Minshall
    Abstract:

    Abstract Albumin transcytosis, a determinant of transendothelial permeability, is mediated by the release of caveolae from the plasma membrane. We addressed the role of Src phosphorylation of the GTPase dynamin-2 in the mechanism of caveolae release and Albumin Transport. Studies were made in microvascular endothelial cells in which the uptake of cholera toxin subunit B, a marker of caveolae, and 125I-Albumin was used to assess caveolae-mediated endocytosis. Albumin binding to the 60-kDa cell surface Albumin-binding protein, gp60, induced Src activation (phosphorylation on Tyr416) within 1 min and resulted in Src-dependent tyrosine phosphorylation of dynamin-2, which increased its association with caveolin-1, the caveolae scaffold protein. Expression of kinase-defective Src mutant interfered with the association between dynamin-2, which caveolin-1 and prevented the uptake of Albumin. Expression of non-Src-phosphorylatable dynamin (Y231F/Y597F) resulted in reduced association with caveolin-1, and in contrast to WT-dynamin-2, the mutant failed to translocate to the caveolin-rich membrane fraction. The Y231F/Y597F dynamin-2 mutant expression also resulted in impaired Albumin and cholera toxin subunit B uptake and reduced transendothelial Albumin Transport. Thus, Src-mediated phosphorylation of dynamin-2 is an essential requirement for scission of caveolae and the resultant transendothelial Transport of Albumin.

  • Evidence for the role of alveolar epithelial gp60 in active transalveolar Albumin Transport in the rat lung.
    The Journal of physiology, 2001
    Co-Authors: T A John, Richard D. Minshall, S M Vogel, K Ridge, C Tiruppathi, A B Malik
    Abstract:

    1. Transcytosis of Albumin, involving the 60 kDa Albumin-binding glycoprotein, gp60, was studied in cultured type II alveolar epithelial cells obtained from rat lungs. 2. Type II cells internalized the interfacial fluorescent dye RH 414, which marks for plasmalemma vesicles. Fluorescent forms of Albumin and anti-gp60 antibody colocalized in the same plasmalemma vesicles. 3. Antibody (100 microg ml(-1)) cross-linking of gp60 for brief periods (15 min) markedly stimulated vesicular uptake of fluorescently tagged Albumin. The caveolar disrupting agent, filipin (10 nM), abolished the stimulated internalization of Albumin. 4. The vast majority of plasmalemmal vesicles carrying Albumin also immunostained for caveolin-1; however, lysosomes did not stain for caveolin-1. Filipin depleted the epithelial cells of the caveolin-1-positive, Albumin-Transporting plasmalemma vesicles. 5. Prolonged (> 1 h) stimulation of type II cells with cross-linking anti-gp60 antibody produced loss of cell-surface gp60 and abolished endocytic Albumin uptake. 6. Transalveolar Transport of Albumin was also studied in the isogravimetric rat lung preparation perfused at 37 degrees C. (125)I-labelled Albumin was instilled into distal airspaces of lungs, and the resulting (125)I-labelled Albumin efflux into the vascular perfusate was determined. 7. Unlabelled Albumin (studied over a range of 0-10 g (100 instilled ml)(-1)) inhibited 40 % of the Transport of labelled Albumin ((5.7 +/- 0.4) x 10(5) counts (instilled ml)(-1)) with an IC(50) value of 0.34 g (100 ml)(-1). 8. Filipin blocked the displacement-sensitive component of (125)I-labelled Albumin Transport, but had no effect on the Transport of the paracellular tracer (3)[H]mannitol. 9. Displacement-sensitive (125)I-labelled Albumin Transport had a significantly greater Q(10) (27-37 degrees C) than the non-displaceable component. 10. Cross-linking of gp60 by antibody instillation stimulated only the displacement-sensitive (125)I-labelled Albumin transalveolar Transport in intact rat lungs. 11. To estimate the Transport capacity of the displacement-sensitive system, the percentage of instilled (125)I-labelled Albumin counts remaining in lung tissue was compared in lungs treated with instillates containing either 0.05 g (100 ml)(-1) unlabelled Albumin or 5 g (100 ml)(-1) unlabelled Albumin. Approximately 25 % of instilled (125)I-labelled Albumin was cleared from the lung preparations per hour by the displacement-sensitive Transport pathway. This component was blocked by filipin.

  • evidence for the role of alveolar epithelial gp60 in active transalveolar Albumin Transport in the rat lung
    The Journal of Physiology, 2001
    Co-Authors: T A John, Richard D. Minshall, S M Vogel, K Ridge, C Tiruppathi, A B Malik
    Abstract:

    The alveolar epithelium represents the rate-limiting barrier to solute and fluid Transport between the pulmonary capillary lumen and distal air spaces (Schneeberger & Karnovsky, 1971; Gorin et al. 1979; Berthiaume et al. 1989). The liquid in contact with the respiratory surface of alveoli is restricted to a thin layer of epithelial lining fluid (ELF). Type I alveolar epithelial cells regulate the ELF composition and volume, which in turn is important for the maintenance of low alveolar surface tension and efficient gas exchange. Relative to blood plasma, this fluid contains lower Na+ and higher K+ concentrations resulting from the activity of a Na+-K+ ionic pump in the basolateral epithelial membrane (Basset et al. 1987; Goodman et al. 1987; Valeyre et al. 1991; Rutschman et al. 1993; Saumon & Basset, 1993) and from passive Na+ Transport through apical Na+ channels (Matalon & O'Brodovich, 1999). The protein concentration in ELF is also found to be lower than that of plasma by a factor of 4 or more depending on the species investigated and methodology employed (Peterson et al. 1990; Peterson et al. 1993; Pusch et al. 1997). Such a steep protein concentration gradient implies the existence of an active Transport process for plasma proteins. In this regard, some investigators have recognized the existence of a monensin- and nocodazole-sensitive protein uptake pathway in alveolar epithelium of intact mammalian lungs (Hastings et al. 1994; Wangensteen et al. 1996); however, the quantitative importance of such uptake for overall alveolar protein clearance remains unclear (see review by Folkesson et al. 1996). Active Transport of protein molecules across endothelial cells was shown, in some instances, to occur by a receptor-mediated process (Vasile et al. 1983; Ghitescu et al. 1986; Descamps et al. 1996). In the pulmonary microvascular endothelium, Albumin bound with high specificity to the 60 kDa Albumin-binding glycoprotein (gp60 or albondin) and was shown to activate Albumin transcytosis through the endothelium (Schnitzer et al. 1988; Schnitzer, 1992; Tiruppathi et al. 1996; Minshall et al. 2000). Cross-linking of gp60 with an anti-gp60 antibody stimulated endocytosis (as measured by fluorescent styryl pyridinium probes) and Albumin uptake (quantified with radiolabelled Albumin) in cultured endothelial cells (Tiruppathi et al. 1997; Niles & Malik, 1999; Minshall et al. 2000). As a transcellular Albumin Transport pathway may also be present in alveolar epithelial cells (Kim et al. 1985), the purpose of the present study was to characterize the Albumin clearance mechanism of the alveolar epithelium with particular reference to the possible role of gp60 in regulating Albumin Transport in the intact lung.

  • lectin binding to gp60 decreases specific Albumin binding and Transport in pulmonary artery endothelial monolayers
    Journal of Cellular Physiology, 1991
    Co-Authors: A Siflingerbirnboim, Jan E Schnitzer, F A Blumenstock, Chien Ping J Shen, Peter J Del Vecchio, A B Malik
    Abstract:

    : The effect of Albumin binding to cultured bovine pulmonary artery endothelial cell (BPAEC) monolayers on the transendothelial flux of 125I-labelled bovine serum Albumin (BSA) was examined to determine its possible role on Albumin transcytosis. The Transport of 125I-BSA tracer across BPAEC grown on gelatin- and fibronectin-coated filters (0.8 microns pore diam.) was affected by the presence of unlabelled BSA in the medium in that transendothelial 125I-BSA permeability decreased, reaching a 40% reduction at BSA concentrations equal to or greater than 5 mg/ml. BSA binding to BPAEC monolayers was saturated at concentration of 10 mg/ml with an apparent binding affinity of 6 x 10(-7) M. In contrast, gelatin added to the medium altered neither 125I-BSA binding nor Transport. Several lectins were tested for their ability to inhibit 125I-BSA binding and Transport. One lectin, Ricinus communis (RCA), reduced 125I-BSA binding by 70% and Transport by 40%. Other lectins, Ulex europaeus, Triticum vulgare, and Glycine max decreased neither 125I-BSA binding nor Transport. The reduction of 125I-BSA Transport by RCA was not observed in the presence of saturating levels of BSA, indicating that RCA influenced only the Albumin-dependent component of Transport. RCA, but not other lectins, precipitated a 60 kDa plasmalemmal glycoprotein from cell lysates of surface radioiodinated BPAEC monolayers. This 60 kDa glycoprotein appears to be the equivalent of gp60 identified previously as an Albumin binding glycoprotein in rat microvascular endothelium. In summary, approximately 40% of Albumin Transport across BPAEC monolayers is dependent on Albumin binding. This component of Albumin Transport is inhibited by 80% by the binding of RCA to gp60. These results suggest that binding of Albumin to gp60 on pulmonary artery endothelial cell membrane is a critical determinant of transendothelial Albumin flux involving mechanisms such as plasmalemmal vesicular transcytosis.

Richard D. Minshall - One of the best experts on this subject based on the ideXlab platform.

  • Regulation of transendothelial permeability by Src kinase.
    Microvascular Research, 2008
    Co-Authors: Guochang Hu, Richard D. Minshall
    Abstract:

    Abstract Transcellular Transport of Albumin from the endothelial lumen to the abluminal perivascular interstitium via caveolae is a primary determinant of basal endothelial permeability. Albumin binding to specific caveolae-associated proteins induces the internalization of caveolae from the endothelial plasma membrane. Albumin-containing caveolae detach from the plasma membrane and traffic to the opposite membrane where they release Albumin into the extravascular space. The events initiating transcytosis have been shown to be tightly regulated by Src family kinases, and thus Src signaling is thought to be a critical “switch” regulating caveolae-mediated transcellular Transport of the plasma protein Albumin. Recently, accumulating evidence indicates the importance of caveolae-mediated Albumin Transport in endothelial hyperpermeability in response to inflammatory stimuli. In this review, we focus on the current understanding of Src signaling in regulating basal permeability and inflammation-evoked increase in transcellular Albumin permeability of the pulmonary endothelium.

  • Role of Src-induced dynamin-2 phosphorylation in caveolae-mediated endocytosis in endothelial cells.
    Journal of Biological Chemistry, 2004
    Co-Authors: Ayesha N. Shajahan, C Tiruppathi, A B Malik, Barbara Timblin, Raudel Sandoval, Richard D. Minshall
    Abstract:

    Abstract Albumin transcytosis, a determinant of transendothelial permeability, is mediated by the release of caveolae from the plasma membrane. We addressed the role of Src phosphorylation of the GTPase dynamin-2 in the mechanism of caveolae release and Albumin Transport. Studies were made in microvascular endothelial cells in which the uptake of cholera toxin subunit B, a marker of caveolae, and 125I-Albumin was used to assess caveolae-mediated endocytosis. Albumin binding to the 60-kDa cell surface Albumin-binding protein, gp60, induced Src activation (phosphorylation on Tyr416) within 1 min and resulted in Src-dependent tyrosine phosphorylation of dynamin-2, which increased its association with caveolin-1, the caveolae scaffold protein. Expression of kinase-defective Src mutant interfered with the association between dynamin-2, which caveolin-1 and prevented the uptake of Albumin. Expression of non-Src-phosphorylatable dynamin (Y231F/Y597F) resulted in reduced association with caveolin-1, and in contrast to WT-dynamin-2, the mutant failed to translocate to the caveolin-rich membrane fraction. The Y231F/Y597F dynamin-2 mutant expression also resulted in impaired Albumin and cholera toxin subunit B uptake and reduced transendothelial Albumin Transport. Thus, Src-mediated phosphorylation of dynamin-2 is an essential requirement for scission of caveolae and the resultant transendothelial Transport of Albumin.

  • Evidence for the role of alveolar epithelial gp60 in active transalveolar Albumin Transport in the rat lung.
    The Journal of physiology, 2001
    Co-Authors: T A John, Richard D. Minshall, S M Vogel, K Ridge, C Tiruppathi, A B Malik
    Abstract:

    1. Transcytosis of Albumin, involving the 60 kDa Albumin-binding glycoprotein, gp60, was studied in cultured type II alveolar epithelial cells obtained from rat lungs. 2. Type II cells internalized the interfacial fluorescent dye RH 414, which marks for plasmalemma vesicles. Fluorescent forms of Albumin and anti-gp60 antibody colocalized in the same plasmalemma vesicles. 3. Antibody (100 microg ml(-1)) cross-linking of gp60 for brief periods (15 min) markedly stimulated vesicular uptake of fluorescently tagged Albumin. The caveolar disrupting agent, filipin (10 nM), abolished the stimulated internalization of Albumin. 4. The vast majority of plasmalemmal vesicles carrying Albumin also immunostained for caveolin-1; however, lysosomes did not stain for caveolin-1. Filipin depleted the epithelial cells of the caveolin-1-positive, Albumin-Transporting plasmalemma vesicles. 5. Prolonged (> 1 h) stimulation of type II cells with cross-linking anti-gp60 antibody produced loss of cell-surface gp60 and abolished endocytic Albumin uptake. 6. Transalveolar Transport of Albumin was also studied in the isogravimetric rat lung preparation perfused at 37 degrees C. (125)I-labelled Albumin was instilled into distal airspaces of lungs, and the resulting (125)I-labelled Albumin efflux into the vascular perfusate was determined. 7. Unlabelled Albumin (studied over a range of 0-10 g (100 instilled ml)(-1)) inhibited 40 % of the Transport of labelled Albumin ((5.7 +/- 0.4) x 10(5) counts (instilled ml)(-1)) with an IC(50) value of 0.34 g (100 ml)(-1). 8. Filipin blocked the displacement-sensitive component of (125)I-labelled Albumin Transport, but had no effect on the Transport of the paracellular tracer (3)[H]mannitol. 9. Displacement-sensitive (125)I-labelled Albumin Transport had a significantly greater Q(10) (27-37 degrees C) than the non-displaceable component. 10. Cross-linking of gp60 by antibody instillation stimulated only the displacement-sensitive (125)I-labelled Albumin transalveolar Transport in intact rat lungs. 11. To estimate the Transport capacity of the displacement-sensitive system, the percentage of instilled (125)I-labelled Albumin counts remaining in lung tissue was compared in lungs treated with instillates containing either 0.05 g (100 ml)(-1) unlabelled Albumin or 5 g (100 ml)(-1) unlabelled Albumin. Approximately 25 % of instilled (125)I-labelled Albumin was cleared from the lung preparations per hour by the displacement-sensitive Transport pathway. This component was blocked by filipin.

  • evidence for the role of alveolar epithelial gp60 in active transalveolar Albumin Transport in the rat lung
    The Journal of Physiology, 2001
    Co-Authors: T A John, Richard D. Minshall, S M Vogel, K Ridge, C Tiruppathi, A B Malik
    Abstract:

    The alveolar epithelium represents the rate-limiting barrier to solute and fluid Transport between the pulmonary capillary lumen and distal air spaces (Schneeberger & Karnovsky, 1971; Gorin et al. 1979; Berthiaume et al. 1989). The liquid in contact with the respiratory surface of alveoli is restricted to a thin layer of epithelial lining fluid (ELF). Type I alveolar epithelial cells regulate the ELF composition and volume, which in turn is important for the maintenance of low alveolar surface tension and efficient gas exchange. Relative to blood plasma, this fluid contains lower Na+ and higher K+ concentrations resulting from the activity of a Na+-K+ ionic pump in the basolateral epithelial membrane (Basset et al. 1987; Goodman et al. 1987; Valeyre et al. 1991; Rutschman et al. 1993; Saumon & Basset, 1993) and from passive Na+ Transport through apical Na+ channels (Matalon & O'Brodovich, 1999). The protein concentration in ELF is also found to be lower than that of plasma by a factor of 4 or more depending on the species investigated and methodology employed (Peterson et al. 1990; Peterson et al. 1993; Pusch et al. 1997). Such a steep protein concentration gradient implies the existence of an active Transport process for plasma proteins. In this regard, some investigators have recognized the existence of a monensin- and nocodazole-sensitive protein uptake pathway in alveolar epithelium of intact mammalian lungs (Hastings et al. 1994; Wangensteen et al. 1996); however, the quantitative importance of such uptake for overall alveolar protein clearance remains unclear (see review by Folkesson et al. 1996). Active Transport of protein molecules across endothelial cells was shown, in some instances, to occur by a receptor-mediated process (Vasile et al. 1983; Ghitescu et al. 1986; Descamps et al. 1996). In the pulmonary microvascular endothelium, Albumin bound with high specificity to the 60 kDa Albumin-binding glycoprotein (gp60 or albondin) and was shown to activate Albumin transcytosis through the endothelium (Schnitzer et al. 1988; Schnitzer, 1992; Tiruppathi et al. 1996; Minshall et al. 2000). Cross-linking of gp60 with an anti-gp60 antibody stimulated endocytosis (as measured by fluorescent styryl pyridinium probes) and Albumin uptake (quantified with radiolabelled Albumin) in cultured endothelial cells (Tiruppathi et al. 1997; Niles & Malik, 1999; Minshall et al. 2000). As a transcellular Albumin Transport pathway may also be present in alveolar epithelial cells (Kim et al. 1985), the purpose of the present study was to characterize the Albumin clearance mechanism of the alveolar epithelium with particular reference to the possible role of gp60 in regulating Albumin Transport in the intact lung.

S.e. Webber - One of the best experts on this subject based on the ideXlab platform.

  • The effects of intraluminal and extraluminal drug application on secretion and smooth muscle tone in the ferret liquid-filled trachea in vitro.
    Pulmonary Pharmacology, 1992
    Co-Authors: S. Kitano, S.e. Webber, U.m. Wells, J.g. Widdicombe
    Abstract:

    Abstract With the ferret liquid-filled trachea in vitro, intraluminal methacholine (MCh), phenylephrine (PE) and histamine (Hist) increased smooth muscle tone and salbutamol (Salb) decreased tone. Lysozyme output was increased by intraluminal MCh and PE. Albumin Transport into the lumen was not altered by intraluminal Hist, Salb or PE. The concentration-response curves for smooth muscle contraction and for lysozyme output to extraluminal MCh lay to the left of those for intraluminal MCh. Indomethacin shifted the smooth-muscle response curves to MCh significantly to the left but did not significantly alter lysozyme output. Extraluminal MCh produced a concentration-dependent increase in Albumin output whilst intraluminal MCh did so in one of three studies. Albumin output in response to MCh was not significantly altered by indomethacin. Thus, MCh has a less potent effect on smooth muscle and lysozyme secretion and, to a lesser extent, on epithelial Albumin Transport when given intraluminally. This may be because the epithelium restricts diffusion of the drug or due to the production of a non-prostanoid factor which inhibits smooth muscle responsiveness. Smooth muscle responsiveness is enhanced by blocking cyclo-oxygenase activity, suggesting MCh-induced release of a prostanoid with relaxant activity.

  • Evidence for an atypical, or β3‐adrenoceptor in ferret tracheal epithelium
    British Journal of Pharmacology, 1992
    Co-Authors: S.e. Webber, Michael J. Stock
    Abstract:

    : 1. A preparation of the ferret trachea in vitro was used to examine the effects of three selective beta-adrenoceptor agonists on lysozyme secretion from submucosal gland serous cells and epithelial Albumin Transport into tracheal mucus following sustained, submaximal stimulation of mucus production with methacholine (20 microM). 2. Prenalterol, salbutamol and BRL 37344 all enhanced methacholine-induced Albumin output. BRL 37344 was 10,000 times more potent than salbutamol, and salbutamol was slightly more potent than prenalterol. The concentrations required to increase Albumin output by 100% (EC100%) were 1.4 nM, 0.7 mM and approximately 1.0 mM for BRL 37344, salbutamol and prenalterol, respectively. All three agonists inhibited methacholine-induced lysozyme output, with salbutamol being 60 times more potent than BRL 37344, and BRL 37344 being approximately 100 times more potent than prenalterol. 3. The selective beta 2-adrenoceptor antagonist, ICI 118551, inhibited the increase in Albumin output produced by BRL 37344, but much more potent at inhibiting the response to salbutamol; the pA2 for ICI 118551 was 5.55 and 7.18 (P less than 0.001) when the agonist was BRL 37344 and salbutamol, respectively. ICI 118551 also attenuated the inhibition of lysozyme output produced by the two agonists, but was 10-30 times more potent at inhibiting this response than the Albumin response to BRL 37344 and salbutamol. 4. The greater potency (4-5 orders of magnitude) of BRL 37344, compared to the beta 1- (prenalterol) and beta 2- (salbutamol) adrenoceptor selective agonists, in stimulating methacholine-induced Albumin Transport suggests that tracheal epithelium possess an atypical, or beta 3-adrenoceptor similar to that previously reported for adipocytes and gastrointestinal smooth muscle. The weak antagonism of the response to BRL 37344 by ICI 118551 would also be consistent with an atypical adrenoceptor mediating the Albumin Transport response. Inhibition of methacholine-induced serous cell lysozyme output would appear to be mediated predominantly by beta2-adrenoceptors.5. In view of the possible beneficial protective effects of Albumin in airway surface liquid, selective beta3-agonists like BRL 37344 might have potential value in the prevention and/or treatment of inflammatory airway disease.

  • Endothelin-1 inhibits pre-stimulated tracheal submucosal gland secretion and epithelial Albumin Transport.
    British Journal of Pharmacology, 1991
    Co-Authors: E. Yurdakos, S.e. Webber
    Abstract:

    : 1. Endothelin-1 potently contracts smooth muscle, including that in the airways. However, its effect on airway mucosal function has not so far been studied. 2. We have used the ferret whole trachea in vitro to examine the effect of endothelin-1 on tracheal smooth muscle tone, transepithelial potential difference (p.d.), submucosal gland secretion (including lysozyme secretion from serous cells) and active epithelial Albumin Transport. In addition we have examined the effects of endothelin on submucosal gland secretion and Albumin Transport pre-stimulated with the muscarinic agonist methacholine and the alpha-adrenoceptor agonist phenylephrine. The effects of the Ca2+ channel blocker nifedipine on the responses to endothelin have also been assessed. 3. Endothelin (0.1-100 nM) produced concentration-dependent increases in intraluminal tracheal pressure indicating smooth muscle contraction, and in the negativity of the transepithelial p.d. These effects were partially inhibited by nifedipine (10 microM). 4. Endothelin (0.01-100 nM) had no significant effect on baseline rates of mucus, lysozyme or Albumin outputs, but produced concentration-dependent reductions in maintained methacholine- and phenylephrine-induced mucus, lysozyme and Albumin outputs. In general endothelin was more potent against methacholine-induced effects. All of the concentration-response curves for endothelin were shallow and some appeared to be biphasic, suggesting the possibility of more than one mechanism of action of endothelin. 5. The effects of endothelin (at concentrations greater than 1 nM) on phenylephrine-induced mucus volume, lysozyme and Albumin outputs were significantly inhibited by nifedipine. Similarly the effect of endothelin (greater than 1 nM) on methacholine-induced mucus volume and Albumin outputs (but not lysozyme output) was attenuated by nifedipine. Similarly the effect of endothelin (>1 nM) on methacholine-induced mucus volume and Albumin outputs (but not lysozyme output) was attenuated by nifedipine. The effects of endothelin (at concentrations

  • The effect of hydrogen peroxide on smooth muscle tone, mucus secretion and epithelial Albumin Transport of the ferret trachea in vitro.
    Pulmonary Pharmacology, 1991
    Co-Authors: T. Morikawa, S.e. Webber, J.g. Widdicombe
    Abstract:

    Abstract The effect of hydrogen peroxide (H 2 O 2 ) was examined on baseline and on methacholine- and phenylephrine-stimulated smooth muscle tone, mucus volume and lysozyme outputs, and epithelial Albumin Transport of the ferret whole trachea in vitro. H 2 O 2 (10 μM–10 mM) had no significant effect on tracheal smooth muscle tone but produced concentration-dependent increases in mucus volume, lysozyme and Albumin outputs. The potential difference (P.D.) across the trachea was not changed by H 2 O 2 . Exposure of the trachea to H 2 O 2 (1 mM) for 2 h reduced the smooth muscle contractions and lysozyme outputs due to methacholine (1 μM) and phenylephrine (10 μM). Methacholine-induced Albumin output was significantly increased by H 2 O 2 but that due to phenylephrine was not significantly affected. Exposure to H 2 O 2 had no significant effect on the mucus volume output produced by methacholine or phenylephrine. Thus H 2 O 2 directly stimulates submucosal gland secretion, including secretion from serous cells, and epithelial Albumin Transport across the ferret trachea but has no effect on tracheal smooth muscle tone. H 2 O 2 reduces methacholine- and phenylephrine-induced smooth muscle contractions and serous cell secretion. H 2 O 2 causes hyperresponsiveness of Albumin output to methacholine but not to phenylephrine.

  • The effects of calcitonin gene‐related peptide on submucosal gland secretion and epithelial Albumin Transport in the ferret trachea in vitro
    British Journal of Pharmacology, 1991
    Co-Authors: S.e. Webber, J.g. Widdicombe
    Abstract:

    1 We have examined the effect of calcitonin gene-related peptide (CGRP) on basal mucus volume, lysozyme and Albumin outputs from the ferret whole trachea in vitro, and on the outputs produced by methacholine and substance P (SP). We have also examined the effect of inhibiting neutral enkephalinase with thiorphan on the responses to CGRP. 2 CGRP (1–100 nm) produced small concentration-dependent increases in basal mucus volume, lysozyme and Albumin outputs. These effects of CGRP were enhanced by thiorphan. The increases in basal outputs with CGRP and the potentiation by thiorphan were considerably less than previously observed with SP and neurokinin A (NKA). CGRP had no significant effect on potential difference (PD) across the trachea. 3 CGRP produced a concentration-dependent inhibition of methacholine- and SP-induced lysozyme output but a concentration-dependent increase in methacholine- and SP-induced Albumin output. The effects of CGRP on methacholine-induced lysozyme and Albumin outputs were enhanced by thiorphan. CGRP weakly inhibited methacholine-induced mucus volume output and weakly enhanced SP-induced mucus volume output. 4 Thus, CGRP weakly stimulates basal serous cell secretion and epithelial Albumin Transport, but does not alter epithelial integrity. CGRP inhibits the serous cell secretion due to methacholine or SP, but potentiates the epithelial Albumin Transport produced by these agents. The interaction between CGRP and other sensory neuropeptides or muscarinic agonists on airway submucosal glands and epithelium may be important in the normal airway and in inflammatory airway diseases where release of sensory neuropeptides is enhanced.

E. M. Renkin - One of the best experts on this subject based on the ideXlab platform.

  • Acute alveolar hypoxia increases blood-to-tissue Albumin Transport: role of atrial natriuretic peptide
    Journal of Applied Physiology, 1997
    Co-Authors: T. S. E. Albert, V. L. Tucker, E. M. Renkin
    Abstract:

    Albert, T. S. E., V. L. Tucker, and E. M. Renkin. Acute alveolar hypoxia increases blood-to-tissue Albumin Transport: role of atrial natriuretic peptide. J. Appl. Physiol. 82(1): 111–117, 1997.—Plasma immunoreactive atrial natriuretic peptide (irANP) and blood-to-tissue clearance of 131 I-labeled rat serum Albumin (C RSA ) were examined in anesthetized rats during hypoxic ventilation ( n = 5–7/group). Hypoxia (10 min) increased irANP from 211 ± 29 (room air) to 229 ± 28 (15% O 2 , not significant), 911 ± 205 (10% O 2 ), and 4,374 ± 961 pg/ml (8% O 2 ), respectively. Graded increases in C RSA were significant at 8% O 2 in fat (3.6-fold), ileum (2.2-fold), abdominal muscles (2.0-fold), kidney (1.8-fold), and jejunum (1.4-fold). C RSA was decreased in back skin and testes; heart, brain, and lungs were unaffected. The increases in C RSA were related to irANP and not to arterial P O 2 . Circulating plasma volume was negatively correlated with whole body C RSA . Graded increases in extravascular water content (EVW) were found in the kidney, left heart, and cerebrum and were positively related to C RSA in the kidney. EVW decreased in gastrointestinal tissues; the magnitude was inversely related to C RSA . We conclude that ANP-induced protein extravasation contributes to plasma volume contraction during acute hypoxia.

  • tissue specific effects of physiological anp infusion on blood tissue Albumin Transport
    American Journal of Physiology-regulatory Integrative and Comparative Physiology, 1992
    Co-Authors: V. L. Tucker, K Simanonok, E. M. Renkin
    Abstract:

    Blood-tissue Transport of 131I-labeled bovine serum Albumin (BSA) during intravenous infusion of synthetic atrial natriuretic peptide (ANP) was examined in anesthetized male Wistar rats. Plasma volumes were maintained at pre-ANP levels by infusion of 2% BSA in lactated Ringer solution (LR) to minimize compensatory responses to ANP-induced hypovolemia. 131I-BSA clearance was measured over 30 min, and 125I-BSA was injected terminally to correct for intravascular volume. Thirty-minute infusion of 20 ng.kg-1.min-1 ANP resulted in a tissue-selective increase in 131I-BSA clearance in jejunum and colon compared with controls given LR only. Smaller but significant increases in tracer clearance also were observed in fat, kidney, left ventricle, and skeletal muscle exposed to 400 ng.kg-1.min-1 ANP. The observed elevation in tracer Albumin extravasation was not associated with any measurable increase in tissue extravascular water content. Furthermore, it was shown that coupling of 131I-BSA Transport to filtration induced by hindlimb venous congestion was similar in control and ANP-treated rats. In a second series of experiments, plasma ANP levels were determined after 30-min ANP infusions from 0 to 180 ng.kg-1.min-1. Significant linear associations between physiological ANP levels (62-578 pg/ml) and 131I-BSA clearance were demonstrable for small intestine, colon, fat, kidney, and skeletal muscle but not for skin, heart, diaphragm, and lung. We conclude that raising plasma ANP by infusion of the synthetic peptide results in a filtration-independent, tissue-selective increase in Albumin Transport. Tissue uptake of Albumin is a potential mechanism for extrarenal fluid shift during circulatory volume overload.

  • Plasma volume expansion with colloids increases blood-tissue Albumin Transport
    American Journal of Physiology-heart and Circulatory Physiology, 1992
    Co-Authors: E. M. Renkin, V. L. Tucker, D. O'loughlin, M. Wong, L. Sibley
    Abstract:

    Extravasation of plasma proteins is increased after volume expansion with whole blood or plasma. To investigate the mechanisms responsible for this phenomenon, we measured extravascular accumulation of exogenous 131I-labeled bovine serum Albumin in several tissues and organs of anesthetized rats. Plasma volume was increased acutely by infusion of isoncotic Albumin or polyvinylpyrrolidone, with or without subsequent infusion of a 1:10 dilution of the colloid to induce blood-to-tissue fluid movement. Controls were given only a slow sustaining infusion of saline. The amounts of fluid and plasma protein lost from the circulation were followed simultaneously by two methods: 1) material balance in the whole animal, and 2) changes in 131I-labeled Albumin uptake (VA) and water content (VW) in the individual tissues. Plasma volume expansion of 80-90% increased plasma protein extravasation in the whole rat by an average of 2.7-fold over a 30-min period. Of the protein extravasated, 42% entered the abdominal cavity. The rest was distributed in the interstitial compartment of various tissues and organs. Tracer Albumin accumulation (averaged over 30 min) was increased 38-82% in skin and paw, 40-59% in skeletal muscles, 131% in hearts, and 167-230% in different parts of the intestine. Increased convective Transport does not appear to be a major factor. There was little or no relation of Albumin Transport increase to the magnitude or direction of net fluid transfer. Coupling of Albumin Transport to volume flow was not greater than previously reported for saline infusion or venous congestion. Convective redistribution (convective Transport without net fluid transfer, “volume recirculation”) is estimated to increase Albumin Transport no more than 10% under the conditions of our experiments. The greater part of the increase is thus dissipative, i.e., attributable to increased diffusion or increased vesicular exchange. Control of dissipative Transport of Albumin may play an important role in regulating plasma volume.