Effect of nedocromil sodium on down-regulation of pulmonary β-adrenoceptors

1. We have studied the effect of the anti-inflammatory anti-asthma drug, nedocromil sodium, on down-regulation of pulmonary β-adrenoceptors in guinea-pig lung. 2. Incubation of minced lung with isoprenaline (10 μmol/l) resulted in a reduction in maximum binding capacity of [125I]iodocyanopindolol to lung membranes from 246 ± 4 to 169 ± 6 fmol/mg of protein (mean ± sem, P < 0.01, n = 18). 3. Nedocromil sodium, which had no direct effect on [125I]iodocyanopindolol binding, prevented isoprenaline-induced down-regulation, giving complete protection at a dose of 100 μmol/l. 4. The mechanism of this effect is not certain, but nedocromil sodium may interfere with the internalization of β-adrenoceptors in pulmonary parenchymal cells. This may have some therapeutic relevance.

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Different zonal distribution of the asialoglycoprotein receptor, the α2-macroglobulin receptor/low-density-lipoprotein receptor-related protein and the lipoprotein-remnant receptor of rat liver parenchymal cells

Biochemical Journal ◽

10.1042/bj3030809 ◽

1994 ◽

Vol 303 (3) ◽

pp. 809-816 ◽

Cited By ~ 11

Author(s):

A H Voorschuur ◽

J Kuiper ◽

J A M Neelissen ◽

W Boers ◽

T J C Van Berkel

Keyword(s):

Binding Capacity ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Low Density ◽

Lipoprotein Receptor ◽

Zonal Distribution ◽

Maximum Binding Capacity ◽

Density Lipoprotein Receptor ◽

Parenchymal Cells ◽

Lipoprotein Receptor Related Protein

Periportal and perivenous parenchymal cells were isolated by the digitonin-pulse perfusion method. The digitonin-pulse perfusion was shown to lead to selective lysis of the correct zone with a straight and sharp border of two to three cells. The mean ratios of alanine aminotransferase activity (a marker for periportal parenchymal cells) and glutamine synthetase activity (a perivenous marker) of periportal to perivenous parenchymal cells were 1.76 and 0.025 respectively. Cells were incubated in vitro with 125I-asialo-orosomucoid (ASOR), 125I-trypsin-activated alpha 2-macroglobulin (alpha 2M-T) or 125I-beta-migrating very-low-density lipoprotein (beta-VLDL), in order to determine the zonal distribution of the asialoglycoprotein receptor (ASGPr), the alpha 2-macroglobulin receptor/low-density-lipoprotein receptor-related protein (alpha 2Mr/LRP) and the lipoprotein-remnant receptor, respectively. Maximum binding capacity for 125I-ASOR on parenchymal cells showed a periportal/perivenous ratio of 0.70. The periportal/perivenous ratio of Bmax. values of binding of 125I-alpha 2M-T to parenchymal cells was 1.51. The Bmax. values of binding of 125I-beta-VLDL, however, were about equal for both cell populations. It is concluded that the maximum binding capacity of the ASGPr on isolated periportal parenchymal cells is 0.70 times that of perivenous parenchymal cells. The 1.51-fold higher expression of the alpha 2Mr/LRP on periportal cells, compared with perivenous parenchymal cells, indicates a zonal specialization for the uptake of the suggested multiple ligands. In contrast, the observed homogeneous distribution of the lipoprotein-remnant receptor is in accordance with the suggestion that lipoprotein remnants bind to a specific receptor, which is different from the alpha 2Mr/LRP. The zonal heterogeneity in the expression of receptors suggests that receptor-dependent uptake pathways are under zonal control, leading to intrahepatic heterogeneity in the removal of ligands from the blood circulation.

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Muscle Na+-K+-ATPase response during 16 h of heavy intermittent cycle exercise

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00004.2007 ◽

2007 ◽

Vol 293 (2) ◽

pp. E523-E530 ◽

Cited By ~ 13

Author(s):

H. J. Green ◽

T. A. Duhamel ◽

G. P. Holloway ◽

J. W. Moule ◽

J. Ouyang ◽

...

Keyword(s):

Aerobic Power ◽

Intermittent Exercise ◽

Binding Capacity ◽

Vastus Lateralis ◽

Intrinsic Activity ◽

Cycle Exercise ◽

Maximum Binding Capacity ◽

Phosphatase Assay ◽

Quantitative Immunoblotting

This study investigated the effects of a 16-h protocol of heavy intermittent exercise on the intrinsic activity and protein and isoform content of skeletal muscle Na+-K+-ATPase. The protocol consisted of 6 min of exercise performed once per hour at ∼91% peak aerobic power (V̇o2 peak) with tissue sampling from vastus lateralis before (B) and immediately after repetitions 1 (R1), 2 (R2), 9 (R9), and 16 (R16). Eleven untrained volunteers with a V̇o2 peak of 44.3 ± 2.3 ml·kg−1·min−1 participated in the study. Maximal Na+-K+-ATPase activity ( Vmax, in nmol·mg protein−1·h−1) as measured by the 3- O-methylfluorescein K+-stimulated phosphatase assay was reduced ( P < 0.05) by ∼15% with exercise regardless of the number of repetitions performed. In addition, Vmax at R9 and R16 was lower ( P < 0.05) than at R1 and R2. Vanadate-facilitated [3H]ouabain determination of Na+-K+-ATPase content (maximum binding capacity, pmol/g wet wt), although unaltered by exercise, increased ( P < 0.05) 8.3% by R9 with no further increase observed at R16. Assessment of relative changes in isoform abundance measured at B as determined by quantitative immunoblotting showed a 26% increase ( P < 0.05) in the α2-isoform by R2 and a 29% increase in α3 by R9. At R16, β3 was lower ( P < 0.05) than at R2 and R9. No changes were observed in α1, β1, or β2. It is concluded that repeated sessions of heavy exercise, although resulting in increases in the α2- and α3-isoforms and decreases in β3-isoform, also result in depression in maximal catalytic activity.

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Nedocromil Sodium Inhibits Hypertonic Saline-induced Plasma Extravasation in Guinea Pig Airways

Biomedical Research ◽

10.2220/biomedres.20.233 ◽

1999 ◽

Vol 20 (4) ◽

pp. 233-238 ◽

Cited By ~ 5

Author(s):

MIKA ONO ◽

TOSHIO ABE ◽

MAKOTO WATANABE ◽

YUMI YAMADA ◽

SHIGEMI YOSHIHARA

Keyword(s):

Guinea Pig ◽

Hypertonic Saline ◽

Nedocromil Sodium ◽

Plasma Extravasation

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Regulation of bombesin receptors on pancreatic acini by cholecystokinin

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1989.256.2.g291 ◽

1989 ◽

Vol 256 (2) ◽

pp. G291-G298

Author(s):

M. Younes ◽

S. A. Wank ◽

R. Vinayek ◽

R. T. Jensen ◽

J. D. Gardner

Keyword(s):

Guinea Pig ◽

Response Curve ◽

Binding Capacity ◽

The Other ◽

Single Class ◽

Pancreatic Acini ◽

Cck Receptors ◽

Cyclic Monophosphate ◽

High Affinity ◽

Bombesin Receptors

When guinea pig pancreatic acini are first incubated with the COOH-terminal octapeptide of cholecystokinin (CCK-8), washed, and then reincubated with 125I-[Tyr4]bombesin (125I-[Tyr4]BN) there is a significant decrease in binding of 125I-[Tyr4]BN compared with that observed with pancreatic acini that have been first incubated with no additions. The CCK-8-induced decrease in binding is maximal after 90 min of first incubation is abolished by reducing the temperature of the first incubation from 37 to 4 degrees C or by adding L364,718 to the first incubation and cannot be reproduced by first incubating acini with A23187, 8-bromoadenosine 3',5'-cyclic monophosphate (8Br-cAMP), 8-bromoadenosine 3',5'-cyclic monophosphate (8Br-cGMP), or 12-O-tetradecanoylphorbol 13-acetate. 125I-[Tyr4]BN interacts with a single class of receptors on pancreatic acini, and first incubating acini with CCK-8 decreases the affinity of BN receptors for BN with no change in the maximal binding capacity. CCK-8 does not alter the rate at which bound 125I-[Tyr4]BN dissociates from pancreatic acini; therefore, CCK-8 must alter the rate at which the radiolabeled BN analogue associates with its receptor. Pancreatic acini possess two classes of CCK receptors: one has a high affinity for CCK-8; the other has a low affinity for CCK-8. The dose-response curve for CCK-8-induced inhibition of binding of 125I-[Tyr4]BN appears to to reflect occupation of low-affinity CCK receptors by CCK-8.(ABSTRACT TRUNCATED AT 250 WORDS)

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Specific binding of serotonin in rat lung

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1985.248.1.e58 ◽

1985 ◽

Vol 248 (1) ◽

pp. E58-E63 ◽

Cited By ~ 1

Author(s):

D. K. Das ◽

H. Steinberg

Keyword(s):

Binding Capacity ◽

Specific Binding ◽

Direct Action ◽

High Capacity ◽

Mitochondrial Fraction ◽

Temperature Sensitive ◽

Inner Mitochondrial Membrane ◽

High Affinity ◽

Single Temperature ◽

Maximum Binding Capacity

Mammalian lungs have been shown to store and to inactivate serotonin (5-HT) by an active process involving uptake and metabolism. 5-HT has direct action on lung including constrictor effects of pulmonary vascular and tracheobronchial smooth muscle, suggesting the presence of 5-HT receptors in lung. We have identified specific 5-HT binding of high affinity to the different lung portions and have shown that there was a different capacity for this binding. Two different 5-HT-binding capacities are present in a purified mitochondrial fraction. Saturation analysis of 5-[3H]HT binding to outer mitochondrial membranes demonstrates a single, temperature-sensitive, high-affinity and high-capacity binding (Kd = 8.3 +/- 1.2 nM, maximum binding capacity = 0.819 +/- 0.046 pmol/mg protein). The dissociation constant of inner mitochondrial membrane demonstrates a low-capacity site (Kd = 25.2 +/- 2.2 nM, maximum binding capacity = 0.453 +/- 0.037 pmol/mg protein). The purified microsomal fraction of lung exhibits a high-capacity binding site for 5-[3H]HT (Kd = 14.8 +/- 1.6 nM, maximum binding capacity = 0.760 +/- 0.03 pmol/mg protein). In addition to the lung being the major site for its inactivation, the presence of several specific 5-HT receptors may be related to some of the known 5-HT actions in lung and may suggest other unknown actions of this amine.

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Growth and hepatic composition in the guinea pig after long-term parenteral hyperalimentation

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1986.251.2.r388 ◽

1986 ◽

Vol 251 (2) ◽

pp. R388-R397 ◽

Cited By ~ 1

Author(s):

C. J. Lu ◽

D. Redmond ◽

R. B. Baggs ◽

A. Schecter ◽

T. A. Gasiewicz

Keyword(s):

Guinea Pig ◽

Lipid Droplets ◽

Morphological Analysis ◽

Basic Research ◽

Serum Chemistry ◽

Glycogen Accumulation ◽

Catheter Implantation ◽

Ad Libitum ◽

Parenchymal Cells

This study examined the feasibility of maintaining male Hartley guinea pigs on long-term hyperalimentation. Data from animals fed ad libitum, but infused with 0.9% saline, indicated that there was minimal effect from catheter implantation, sepsis, or the infusion of large volumes of fluid. This group compared with animals fed and watered ad libitum demonstrated a nearly identical growth rate (6.33 +/- 1.18 and 6.12 +/- 1.32 g/day, respectively), serum chemistry, tissue weights, and hepatic composition and morphology. Animals infused with a total parenteral diet demonstrated growth rates of 4.06 +/- 1.46 g/day for up to 25 days. Loss of infused animals was due in varying degrees to sepsis, mechanical failure, improper placement of the cannula, loss of patency, and death from unknown causes. Morphological analysis of animals fed by total parenteral nutrition revealed an altered distribution and increased size of lipid droplets in hepatic parenchymal and Kupffer cells and glycogen accumulation by the parenchymal cells. Decreased hepatic content of total protein and lipid, as well as cytochrome P450, was also observed. Similarly, serum values of triglyceride were decreased in animals fed by the total parenteral diet. This study indicated that the guinea pig fed by hyperalimentation may be a useful animal model for a number of clinical and basic research applications.

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Distribution of opioid receptors in canine small intestine: implications for function

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1989.256.6.g966 ◽

1989 ◽

Vol 256 (6) ◽

pp. G966-G974 ◽

Cited By ~ 6

Author(s):

H. D. Allescher ◽

S. Ahmad ◽

P. Kostka ◽

C. Y. Kwan ◽

E. E. Daniel

Keyword(s):

Small Intestine ◽

Binding Sites ◽

Myenteric Plexus ◽

Plasma Membranes ◽

Binding Capacity ◽

Opiate Receptors ◽

Circular Muscle ◽

Maximum Binding Capacity ◽

Opiate Binding ◽

Subtype Selective

Distribution of the binding sites for [3H]diprenorphine, a non-selective opiate ligand, was studied in membrane fractions from longitudinal muscle/myenteric plexus and circular muscle containing deep muscular plexus. [3H]saxitoxin was used as a marker for neuronal plasma membranes and 5'-nucleotidase as a marker for smooth muscle plasma membranes. Saxitoxin binding correlated strongly with diprenorphine binding, but 5'-nucleotidase correlated poorly with diprenorphine or saxitoxin binding in these fractions. Opiate binding sites in membranes of myenteric and deep muscular plexus were of high affinity (Kd = 0.12 and 0.18 nM, respectively) with maximum binding capacity of 400 and 500 fmol/mg protein, respectively. Competition experiments using subtype-selective opiate ligands indicated that all three subtypes of opiate receptors were present in the same ratio of 40-45% mu-subtypes, 40-45% delta-subtypes, and 10-15% kappa-subtypes on both plexuses. Opiate receptors of canine small intestine, therefore, are located primarily or exclusively on nerves with similar distributions in nerve membranes containing only axonal varicosities (deep muscular plexus) as in those containing neurons, dendrites, and varicosities (myenteric plexus).

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ATP-MgCl2 treatment after trauma-hemorrhage/resuscitation increases hepatocyte P2-purinoceptor binding capacity

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1994.266.6.r1810 ◽

1994 ◽

Vol 266 (6) ◽

pp. R1810-R1815

Author(s):

M. S. Mahmoud ◽

P. Wang ◽

S. R. Hootman ◽

S. S. Reich ◽

I. H. Chaudry

Keyword(s):

Binding Capacity ◽

Scatchard Analysis ◽

Binding Characteristics ◽

Beneficial Effects ◽

High Affinity ◽

Receptor Component ◽

Receptor Dynamics ◽

Maximum Binding Capacity ◽

High Affinity Receptor ◽

Affinity Receptor

Although our studies indicate that P2-purinoceptor binding capacity decreases after hemorrhage and resuscitation, it is not known whether ATP-MgCl2 administration after hemorrhage has any beneficial effects on the receptor dynamics. To study this, we performed laparotomy (i.e., trauma induced) on rats and bled them to and maintained them at a mean arterial pressure of 40 mmHg until 40% of maximum bleedout volume was returned in the form of Ringer lactate (RL). The animals were then resuscitated with 3 times the volume of maximum bleedout with RL over 45 min followed by 2 times RL along with ATP-MgCl2 (50 mumol/kg body wt) over 95 min. Hepatocytes were isolated at 4, 17, and 27 h after resuscitation. P2-purinoceptor binding characteristics were determined by using [alpha-35S]ATP. Scatchard analysis revealed high-affinity and low-affinity receptor components in the hepatocytes isolated from sham-operated or hemorrhaged animals with or without ATP-MgCl2 infusion. ATP-MgCl2 ameliorated and subsequently restored the decreased maximum binding capacity (Bmax) of the high-affinity receptor component and significantly improved Bmax of the low-affinity receptor component. ATP-MgCl2 administration also produced a progressive enhancement in the affinity of the low-affinity receptor component. Thus the beneficial effects of ATP-MgCl2 observed after trauma-hemorrhage and resuscitation may be, in part, due to the restoration of P2-purinoceptor binding capacity and the enhancement of the receptor affinity.

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Isoproterenol Improves Secretion of Transplanted Submandibular Glands

Journal of Dental Research ◽

10.1177/0022034509337114 ◽

2009 ◽

Vol 88 (5) ◽

pp. 477-482 ◽

Cited By ~ 7

Author(s):

Y.M. Li ◽

Y. Zhang ◽

L. Shi ◽

B. Xiang ◽

X. Cong ◽

...

Keyword(s):

Submandibular Gland ◽

Binding Capacity ◽

Keratoconjunctivitis Sicca ◽

Acinar Cells ◽

Salivary Flow ◽

Secretory Function ◽

Receptor Signal ◽

Maximum Binding Capacity ◽

Wharton’S Duct ◽

Structural Injury

Autotransplantation of the submandibular gland is effective for severe keratoconjunctivitis sicca. However, most transplants show decreased secretion shortly after the operation, which leads to obstruction of Wharton’s duct. The hypothesis that decreased catecholamine release due to denervation contributes to hypofunction in the early phase was tested in transplanted glands in rabbits. We found that salivary flow, expression of β1- and β2-adrenoceptor, and the maximum binding capacity were markedly decreased in the transplanted glands. Isoproterenol significantly reversed the decreased secretion, enhanced the expressions of β1- and β2-adrenoceptor, and ameliorated the atrophy of acinar cells. The contents of cAMP and phospho-ERK 1/2 were increased after isoproterenol treatment. These results indicate that lack of β-adrenoceptor stimulation is involved in early dysfunction of the transplanted gland. Isoproterenol treatment moderates structural injury and improves secretory function in the transplanted submandibular gland through up-regulating β1- and β2-adrenoceptor expression and post-receptor signal transduction.

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