Receptor transactivation cascades. Focus on “Effects of α1D-adrenergic receptors on shedding of biologically active EGF in freshly isolated lacrimal gland epithelial cells”

2007 ◽  
Vol 292 (1) ◽  
pp. C1-C3 ◽  
Author(s):  
Ashley C. Snider ◽  
Kathryn E. Meier
Keyword(s):  
Epithelial Cells ◽  
Lacrimal Gland ◽  
Adrenergic Receptors ◽  
Biologically Active ◽  
Receptor Transactivation

scholarly journals Effects of α1D-adrenergic receptors on shedding of biologically active EGF in freshly isolated lacrimal gland epithelial cells

2006 ◽  
Vol 291 (5) ◽  
pp. C946-C956 ◽  
Author(s):  
LiLi Chen ◽  
Robin R. Hodges ◽  
Chika Funaki ◽  
Driss Zoukhri ◽  
Robert J. Gaivin ◽  
...  
Keyword(s):  
Growth Factors ◽  
Protein Secretion ◽  
Lacrimal Gland ◽  
Adrenergic Receptors ◽  
Egf Receptor ◽  
Cultured Cells ◽  
Biologically Active ◽  
Ectodomain Shedding ◽  
Egf Receptors ◽  
Isolated Cells

Transactivation of EGF receptors by G protein-coupled receptors is a well-known phenomenon. This process involves the ectodomain shedding of growth factors in the EGF family by matrix metalloproteinases. However, many of these studies employ transformed and/or cultured cells that overexpress labeled growth factors. In addition, few studies have shown that EGF itself is the growth factor that is shed and is responsible for transactivation of the EGF receptor. In this study, we show that freshly isolated, nontransformed lacrimal gland acini express two of the three known α1-adrenergic receptors (ARs), namely, α1B- and α1D-ARs. α1D-ARs mediate phenylephrine (an α1-adrenergic agonist)-induced protein secretion and activation of p42/p44 MAPK, because the α1D-AR inhibitor BMY-7378, but not the α1A-AR inhibitor 5-methylurapidil, inhibits these processes. Activation of p42/p44 MAPK occurs through transactivation of the EGF receptor, which is inhibited by the matrix metalloproteinase ADAM17 inhibitor TAPI-1. In addition, phenylephrine caused the shedding of EGF from freshly isolated acini into the buffer. Incubation of freshly isolated cells with conditioned buffer from cells treated with phenylephrine resulted in activation of the EGF receptor and p42/p44 MAPK. The EGF receptor inhibitor AG1478 and an EGF-neutralizing antibody blocked this activation of p42/p44 MAPK. We conclude that in freshly isolated lacrimal gland acini, α1-adrenergic agonists activate the α1D-AR to stimulate protein secretion and the ectodomain shedding of EGF to transactivate the EGF receptor, potentially via ADAM17, which activates p42/p44 MAPK to negatively modulate protein secretion.

scholarly journals Thymic hormone-containing cells. V. Immunohistological detection of metallothionein within the cells bearing thymulin (a zinc-containing hormone) in human and mouse thymuses.

1984 ◽  
Vol 32 (9) ◽  
pp. 942-946 ◽  
Author(s):  
W Savino ◽  
P C Huang ◽  
A Corrigan ◽  
S Berrih ◽  
M Dardenne
Keyword(s):  
Epithelial Cells ◽  
Biologically Active ◽  
Thymic Epithelial Cells ◽  
Cell Organelles ◽  
Thymic Hormone ◽  
Double Labeling ◽  
Active Structure ◽  
Transitional Metals ◽  
Zinc Storage ◽  
High Binding Affinity

Using an immunofluorescence (IF) assay, the presence of metallothionein (MT) was investigated in sections of normal and pathologic human thymuses as well as in cultures of thymic epithelial cells. This protein, known to have a high binding affinity for class II B transitional metals, such as zinc, was detected in the epithelial component of the thymus. Moreover, double labeling experiments with the anti-MT and an anti-thymulin monoclonal antibody showed that all cells containing thymulin, a thymic hormone whose active structure is known to contain zinc, also exhibited large amounts of metallothionein. These results, together with the fact that zinc and thymulin have been detected in the same type of cell organelles, lead to the conclusion that the MT present in thymic epithelial cells might be involved in the mechanism of zinc storage in these cells, thus favoring the secretion of thymulin in its biologically active, zinc-containing form.

Transgenic overexpression of β2-adrenergic receptors in airway epithelial cells decreases bronchoconstriction

2000 ◽  
Vol 279 (2) ◽  
pp. L379-L389 ◽  
Author(s):  
Dennis W. McGraw ◽  
Susan L. Forbes ◽  
Judith C. W. Mak ◽  
David P. Witte ◽  
Patricia E. Carrigan ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Airway Epithelium ◽  
Adrenergic Receptors ◽  
Airway Epithelial Cells ◽  
Airway Responsiveness ◽  
Ozone Exposure ◽  
Clara Cell ◽  
Whole Body ◽  
Airway Epithelial

Airway epithelial cells express β2-adrenergic receptors (β2-ARs), but their role in regulating airway responsiveness is unclear. With the Clara cell secretory protein (CCSP) promoter, we targeted expression of β2-ARs to airway epithelium of transgenic (CCSP-β2-AR) mice, thereby mimicking agonist activation of receptors only in these cells. In situ hybridization confirmed that transgene expression was confined to airway epithelium, and autoradiography showed that β2-AR density in CCSP-β2-AR mice was approximately twofold that of nontransgenic (NTG) mice. Airway responsiveness measured by whole body plethysmography showed that the methacholine dose required to increase enhanced pause to 200% of baseline (ED200) was greater for CCSP-β2-AR than for NTG mice (345 ± 34 vs. 157 ± 14 mg/ml; P < 0.01). CCSP-β2-AR mice were also less responsive to ozone (0.75 ppm for 4 h) because enhanced pause in NTG mice acutely increased to 77% over baseline ( P < 0.05) but remained unchanged in the CCSP-β2-AR mice. Although both groups were hyperreactive to methacholine 6 h after ozone exposure, the ED200for ozone-exposed CCSP-β2-AR mice was equivalent to that for unexposed NTG mice. These findings show that epithelial cell β2-ARs regulate airway responsiveness in vivo and that the bronchodilating effect of β-agonists results from activation of receptors on both epithelial and smooth muscle cells.

Expression of mRNA for natriuretic peptide receptor subtypes in bovine kidney

1994 ◽  
Vol 267 (2) ◽  
pp. F318-F324 ◽  
Author(s):  
T. Yamamoto ◽  
L. Feng ◽  
T. Mizuno ◽  
S. Hirose ◽  
K. Kawasaki ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Natriuretic Peptide ◽  
Collecting Duct ◽  
Biologically Active ◽  
Ribonuclease Protection Assay ◽  
Receptor Subtypes ◽  
Total Rna ◽  
Duct Cells ◽  
Glomerular Epithelial Cells ◽  
Collecting Duct Cells

The localization of mRNA for atrial natriuretic peptide (ANP) receptor subtypes (A, B, C) in the kidney was examined. Quantitative analysis of the ribonuclease protection assay showed that the numbers of type A receptor (ANPRA) mRNA were 6.9 x 10(7) in the glomeruli and 10.4 x 10(7) molecules/micrograms of total RNA in the inner medulla, and that of type C receptor (ANPRC) mRNA was 21.7 x 10(7) molecules/micrograms of total RNA in the glomeruli. The type B receptor (ANPRB) mRNA was present in smaller numbers (4.5-4.9 x 10(6) molecules/micrograms of total RNA) evenly throughout the kidney fractions. In situ hybridization demonstrated both ANPRA and ANPRC mRNA selectively in the glomerular epithelial cells and ANPRA mRNA in the collecting duct cells of the inner medulla. ANPRC was also localized on the foot processes of glomerular epithelial cells by immunohistochemistry using a specific antibody against the receptor. These results indicate that ANPRA is the major biologically active receptor for the ANP family of hormones in the kidney and is present selectively on the glomerular epithelial cells and inner medullary collecting duct cells. These cells are presumed to play a role in the regulation of glomerular filtration rate and sodium excretion induced by the family of ANP.

scholarly journals Agonist binding to β-adrenergic receptors on human airway epithelial cells inhibits migration and wound repair

2015 ◽  
Vol 309 (12) ◽  
pp. C847-C855 ◽  
Author(s):  
Elizabeth R. Peitzman ◽  
Nathan A. Zaidman ◽  
Peter J. Maniak ◽  
Scott M. O'Grady
Keyword(s):  
Epithelial Cells ◽  
Protein Phosphatase ◽  
Adrenergic Receptors ◽  
Wound Repair ◽  
Wound Closure ◽  
Basal Membrane ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Phosphatase 2A ◽  
Β Adrenergic Receptors

Human airway epithelial cells express β-adrenergic receptors (β-ARs), which regulate mucociliary clearance by stimulating transepithelial anion transport and ciliary beat frequency. Previous studies using airway epithelial cells showed that stimulation with isoproterenol increased cell migration and wound repair by a cAMP-dependent mechanism. In the present study, impedance-sensing arrays were used to measure cell migration and epithelial restitution following wounding of confluent normal human bronchial epithelial (NHBE) and Calu-3 cells by electroporation. Stimulation with epinephrine or the β2-AR-selective agonist salbutamol significantly delayed wound closure and reduced the mean surface area of lamellipodia protruding into the wound. Treatment with the β-AR bias agonist carvedilol or isoetharine also produced a delay in epithelial restitution similar in magnitude to epinephrine and salbutamol. Measurements of extracellular signal-regulated kinase phosphorylation following salbutamol or carvedilol stimulation showed no significant change in the level of phosphorylation compared with untreated control cells. However, inhibition of protein phosphatase 2A activity completely blocked the delay in wound closure produced by β-AR agonists. In Calu-3 cells, where CFTR expression was inhibited by RNAi, salbutamol did not inhibit wound repair, suggesting that β-AR agonist stimulation and loss of CFTR function share a common pathway leading to inhibition of epithelial repair. Confocal images of the basal membrane of Calu-3 cells labeled with anti-β1-integrin (clone HUTS-4) antibody showed that treatment with epinephrine or carvedilol reduced the level of activated integrin in the membrane. These findings suggest that treatment with β-AR agonists delays airway epithelial repair by a G protein- and cAMP-independent mechanism involving protein phosphatase 2A and a reduction in β1-integrin activation in the basal membrane.

scholarly journals Adrenergic and Cholinergic Receptors of Cerebral Microvessels

1981 ◽  
Vol 1 (3) ◽  
pp. 329-338 ◽  
Author(s):  
Sami I. Harik ◽  
Virendra K. Sharma ◽  
John R. Wetherbee ◽  
Robert H. Warren ◽  
Shailesh P. Banerjee
Keyword(s):  
Adrenergic Receptors ◽  
Specific Binding ◽  
Cholinergic Receptors ◽  
Biologically Active ◽  
Adrenergic Agonists ◽  
Muscarinic Cholinergic Receptors ◽  
Cerebral Microvessels ◽  
Binding Characteristics ◽  
Muscarinic Cholinergic ◽  
Β Adrenergic Receptors

The presence of α- and β-adrenergic and muscarinic cholinergic receptors in cerebral microvessels of the rat and pig was assessed by ligand binding techniques. The results demonstrate the presence of specific binding to α2- and β-adrenergic receptors but no appreciable specific binding to α1-adrenergic or muscarinic cholinergic receptors. β-Adrenergic receptors of pig cerebral microvessels are similar to those of the brain and other organs in their binding characteristics to the tritiated ligand and in their stereospecificity of binding to the biologically active isomers of β-adrenergic agonists. Further evidence derived from the differential potency of binding displacement by the various β-adrenergic agonists and selective β1- and β2-adrenergic antagonists indicates that β-adrenergic receptors of pig cerebral microvessels are mostly of the β2-subtype.

scholarly journals Role of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Epithelial–Mesenchymal Transition

2019 ◽  
Vol 20 (19) ◽  
pp. 4813 ◽  
Author(s):  
Sevindzh Kletukhina ◽  
Olga Neustroeva ◽  
Victoria James ◽  
Albert Rizvanov ◽  
Marina Gomzikova
Keyword(s):  
Epithelial Cells ◽  
Extracellular Vesicles ◽  
Intercellular Communication ◽  
Epithelial Mesenchymal Transition ◽  
Genetic Material ◽  
Biologically Active ◽  
Target Cells ◽  
Mesenchymal Transition ◽  
New Evidence

Epithelial–mesenchymal transition (EMT) is a process that takes place during embryonic development, wound healing, and under some pathological processes, including fibrosis and tumor progression. The molecular changes occurring within epithelial cells during transformation to a mesenchymal phenotype have been well studied. However, to date, the mechanism of EMT induction remains to be fully elucidated. Recent findings in the field of intercellular communication have shed new light on this process and indicate the need for further studies into this important mechanism. New evidence supports the hypothesis that intercellular communication between mesenchymal stroma/stem cells (MSCs) and resident epithelial cells plays an important role in EMT induction. Besides direct interactions between cells, indirect paracrine interactions by soluble factors and extracellular vesicles also occur. Extracellular vesicles (EVs) are important mediators of intercellular communication, through the transfer of biologically active molecules, genetic material (mRNA, microRNA, siRNA, DNA), and EMT inducers to the target cells, which are capable of reprogramming recipient cells. In this review, we discuss the role of intercellular communication by EVs to induce EMT and the acquisition of stemness properties by normal and tumor epithelial cells.

Protein secretion induced by isoproterenol or pentoxifylline in lacrimal gland: Ca2+ effects

1984 ◽  
Vol 246 (1) ◽  
pp. C37-C44 ◽  
Author(s):  
P. Mauduit ◽  
G. Herman ◽  
B. Rossignol
Keyword(s):  
Protein Secretion ◽  
Lacrimal Gland ◽  
Adrenergic Receptors ◽  
Time Course ◽  
Phosphodiesterase Inhibitor ◽  
Extracellular Calcium ◽  
Maximal Response ◽  
Beta Adrenergic Receptors ◽  
Beta Adrenergic ◽  
Camp Analogue

In exorbital lacrimal glands, pentoxifylline (a methylxanthine) induces labeled protein secretion in a dose-related manner: the half-maximal and maximal stimulations are at 4 and 10 mM, respectively. In the presence of papaverine (10(-5) M), a phosphodiesterase inhibitor, labeled protein discharge is strongly stimulated by isoproterenol, via beta-adrenergic receptors: the maximal response is at 10(-6) M. l-Propranolol specifically inhibits the secretory stimulation to isoproterenol in a dose-related manner: for 5 X 10(-6) M isoproterenol in the presence of 10(-5) M papaverine, the half-maximal and maximal inhibitions are at 3 X 10(-7) and 10(-5) M, respectively. The beta-adrenergic response is mimicked by the adenosine 3',5'-cyclic monophosphate (cAMP) analogue dibutyryl cAMP (DBcAMP) at a 10(-3) M concentration. The time course of labeled protein secretion induced by pentoxifylline, DBcAMP, and isoproterenol shows a latency. In the presence or absence of extracellular calcium, pentoxifylline and isoproterenol immediately increase the cAMP intracellular level. Extracellular calcium omission increases the observed latency and also affects the maximal rate of protein secretion. As opposed to the cholinergic agonist, pentoxifylline has only a slight but sustained effect on 45Ca efflux, whereas isoproterenol has none. These data suggest that labeled protein secretion, such as that of peroxidase, can also be stimulated in rat exorbital lacrimal gland, through beta-adrenergic receptors; in the stimulation evoked by a beta-adrenergic agonist, DBcAMP, or methylxanthine, calcium could play a key role.

scholarly journals Extracts and Marine Algae Polysaccharides in Therapy and Prevention of Inflammatory Diseases of the Intestine

Marine Drugs ◽  
2020 ◽  
Vol 18 (6) ◽  
pp. 289 ◽  
Author(s):  
Natalya N. Besednova ◽  
Tatyana S. Zaporozhets ◽  
Tatyana A. Kuznetsova ◽  
Ilona D. Makarenkova ◽  
Sergey P. Kryzhanovsky ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Inflammatory Diseases ◽  
Food Additives ◽  
Therapeutic Targets ◽  
Public Health Problem ◽  
Structural Features ◽  
Biologically Active ◽  
Molecular Weights ◽  
Adverse Health Effects ◽  
Treatment And Prevention

Inflammatory bowel disease (IBD) is a serious public health problem worldwide. Current therapeutic strategies that use anti-inflammatory drugs, immunosuppressants, and biological treatments are often ineffective and have adverse health effects. In this regard, the use of natural compounds aimed at key pathogenic therapeutic targets in IBD attracts universal attention. Seaweed is a valuable source of structurally diverse biologically active compounds. The materials presented in the review indicate that seaweed extracts and polysaccharides are effective candidates for the development of drugs, biological food additives, and functional nutrition products for the treatment and prevention of IBD. The structural features of algal polysaccharides provide the possibility of exposure to therapeutic targets of IBD, including proinflammatory cytokines, chemokines, adhesion molecules, nuclear factor NF-kB, intestinal epithelial cells, reactive oxygen and nitrogen. Further study of the relationship between the effect of polysaccharides from different types of algae, with different structure and molecular weights on immune and epithelial cells, intestinal microorganisms will contribute to a deeper understanding of their mechanisms and will help in the development of drugs, dietary supplements, functional foods for the treatment of patients with IBD.

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