Ectopic olfactory receptors in the respiratory system

2020 ◽  
Vol 29 (6) ◽  
pp. 734-738
Author(s):  
V. N. Mineev
Keyword(s):  
Smooth Muscle ◽  
Olfactory Receptor ◽  
Olfactory Receptors ◽  
Receptor Activation ◽  
Neuroendocrine Cells ◽  
Receptor Expression ◽  
Special Role ◽  
Concentration Data ◽  
Cell Functions

New findings and concepts on a role of so-called “ectopic” chemosensory receptors arise recently. The ectopic receptors are expressed outside their classical localization (nasal cavity) and referred to as extra-nasal olfactory receptors. Functional investigations of the ectopic olfactory receptors in the lungs are also ongoing. To date, it is well-known that molecules of odorous substances (odorants) bind to the G-protein-associated olfactory receptor (Gαolf) that can activate type III adenylate cyclase and increase concentration of a secondary messenger, cyclic adenosine monophosphate (cAMP). In turn, this induces the opening of cAMP-dependent cationic channels including calcium channels. Olfactory receptor activation in neuroendocrine cells of the lungs affected serotonin release which decreased after the stimulation of those cells by an odorant. Amyl butyrate and burgenal, agonists of OR2AG1 and OR1D2 olfactory receptors, respectively, affect smooth muscle contractibility in human bronchi. Amyl butyrate inhibits histamine-induces muscle contractibility, whereas burgenal increases the smooth muscle contractibility. Both the processes are mediated by cAMP-dependent increase in the intracellular calcium concentration. Data have been published about the receptor expression on immune cells such as monocytes, natural killers, T- and B-lymphocites, and polymorphonuclears. Ectopic olfactory receptors are thought to participate in modulation (controlling) of intrinsic cell functions which provide a special role of inflammatory cells in asthma. In future, the olfactory receptor modulation could be probably used as a novel therapeutic approach in asthma and other chronic inflammatory lung diseases.

scholarly journals An autoantibody directed against human thrombin anion-binding exosite in a patient with arterial thrombosis: effects on platelets, endothelial cells, and protein C activation

Blood ◽  
1994 ◽  
Vol 84 (6) ◽  
pp. 1843-1850 ◽  
Author(s):  
E Arnaud ◽  
M Lafay ◽  
P Gaussem ◽  
V Picard ◽  
M Jandrot-Perrus ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Arterial Thrombosis ◽  
Protein C ◽  
Receptor Activation ◽  
Anion Binding ◽  
Thrombin Receptor ◽  
Cell Functions ◽  
Human Thrombin

Abstract An autoantibody, developed by a patient with severe and recurrent arterial thrombosis, was characterized to be directed against the anion- binding exosite of thrombin, and inhibited all thrombin interactions requiring this secondary binding site without interfering with the catalytic site. The effect of the antibody was studied on thrombin interactions with platelets and endothelial cells from human umbilical veins (HUVEC). The autoantibody specifically and concentration- dependently inhibited alpha-thrombin-induced platelet activation and prostacyclin (PGI2) synthesis from HUVEC. It had no effect when gamma- thrombin or the thrombin receptor activation peptide SFLLR were the inducers. The effect of the antibody on protein C activation has been studied. The antibody blocked the thrombin-thrombomodulin activation of protein C. The inhibition of the activation was maximal with a low concentration of thrombomodulin. The fact that the autoantibody inhibited concentration-dependent alpha-thrombin-induced platelet and endothelial cell functions emphasizes the crucial role of the anion- binding exosite of thrombin to activate its receptor. In regard to the pathology, the antibody inhibited two vascular processes implicated in thrombin-antithrombotic functions, PGI2 secretion, and protein C activation, which could be implicated in this arterial thrombotic disease.

Functional role of miRNA-34A in smooth muscle cell functions and neointima formation

2016 ◽  
Vol 244 ◽  
pp. e3-e4 ◽  
Author(s):  
F. Yang ◽  
Q. Chen ◽  
G. Wen ◽  
C. Zhang ◽  
L.A. Luong ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Functional Role ◽  
Neointima Formation ◽  
Cell Functions

The role of the extracellular loops of the CGRP receptor, a family B GPCR

2012 ◽  
Vol 40 (2) ◽  
pp. 433-437 ◽  
Author(s):  
James Barwell ◽  
Michael J. Woolley ◽  
Mark Wheatley ◽  
Alex C. Conner ◽  
David R. Poyner
Keyword(s):  
Surface Expression ◽  
Receptor Activation ◽  
Receptor Expression ◽  
Cell Surface Expression ◽  
Calcitonin Receptor ◽  
Transmembrane Helices ◽  
Extracellular Loops ◽  
Calcitonin Gene ◽  
G Protein Coupled

The CGRP (calcitonin gene-related peptide) receptor is a family B GPCR (G-protein-coupled receptor). It consists of a GPCR, CLR (calcitonin receptor-like receptor) and an accessory protein, RAMP1 (receptor activity-modifying protein 1). RAMP1 is needed for CGRP binding and also cell-surface expression of CLR. There have been few systematic studies of the ECLs (extracellular loops) of family B GPCRs. However, they are likely to be especially important for the interaction of the N-termini of the peptide agonists that are the natural agonists for these receptors. We have carried out alanine scans on all three ECLs of CLR, as well as their associated juxtamembrane regions. Residues within all three loops influence CGRP binding and receptor activation. Mutation of Ala203 and Ala206 on ECL1 to leucine increased the affinity of CGRP. Residues at the top of TM (transmembrane) helices 2 and 3 influenced CGRP binding and receptor activation. L351A and E357A in TM6/ECL3 reduced receptor expression and may be needed for CLR association with RAMP1. ECL2 seems especially important for CLR function; of the 16 residues so far examined in this loop, eight residues reduce the potency of CGRP at stimulating cAMP production when mutated to alanine.

scholarly journals An autoantibody directed against human thrombin anion-binding exosite in a patient with arterial thrombosis: effects on platelets, endothelial cells, and protein C activation

Blood ◽  
1994 ◽  
Vol 84 (6) ◽  
pp. 1843-1850
Author(s):  
E Arnaud ◽  
M Lafay ◽  
P Gaussem ◽  
V Picard ◽  
M Jandrot-Perrus ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Arterial Thrombosis ◽  
Protein C ◽  
Receptor Activation ◽  
Anion Binding ◽  
Thrombin Receptor ◽  
Cell Functions ◽  
Human Thrombin

An autoantibody, developed by a patient with severe and recurrent arterial thrombosis, was characterized to be directed against the anion- binding exosite of thrombin, and inhibited all thrombin interactions requiring this secondary binding site without interfering with the catalytic site. The effect of the antibody was studied on thrombin interactions with platelets and endothelial cells from human umbilical veins (HUVEC). The autoantibody specifically and concentration- dependently inhibited alpha-thrombin-induced platelet activation and prostacyclin (PGI2) synthesis from HUVEC. It had no effect when gamma- thrombin or the thrombin receptor activation peptide SFLLR were the inducers. The effect of the antibody on protein C activation has been studied. The antibody blocked the thrombin-thrombomodulin activation of protein C. The inhibition of the activation was maximal with a low concentration of thrombomodulin. The fact that the autoantibody inhibited concentration-dependent alpha-thrombin-induced platelet and endothelial cell functions emphasizes the crucial role of the anion- binding exosite of thrombin to activate its receptor. In regard to the pathology, the antibody inhibited two vascular processes implicated in thrombin-antithrombotic functions, PGI2 secretion, and protein C activation, which could be implicated in this arterial thrombotic disease.

scholarly journals Leukotriene Receptors: Crucial Components in Vascular Inflammation

2007 ◽  
Vol 7 ◽  
pp. 1422-1439 ◽  
Author(s):  
Magnus Bäck
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Vascular Inflammation ◽  
Vascular Wall ◽  
Receptor Activation ◽  
Receptor Expression ◽  
Surface Receptors ◽  
Beneficial Effects

The accumulation of immune cells during vascular inflammation leads to formation of leukotrienes (LTs). While macrophages represent a major source of LT biosynthesis in the proximity of the vascular wall, activated T lymphocytes may, in addition, play a key regulatory role on macrophage expression of LT-forming enzymes. Within the vascular wall, LTs activate cell surface receptors of the BLT and CysLT subtypes expressed on vascular smooth muscle and endothelial cells. The LT receptor expression on those cells is highly dependent on transcriptional regulation by pro- and anti-inflammatory mediators. LT receptor activation on vascular smooth muscle cells is associated with both directly and indirectly induced vasoconstriction, as well as intimal hyperplasia through stimulation of migration and proliferation. On the other hand, endothelial LT receptors induce vasorelaxation and leukocyte recruitment and adhesion. Results fromin vitroandin vivostudies of LT receptor antagonists indicate potential beneficial effects in atherosclerosis and other inflammatory cardiovascular diseases.

Inflammation influences vascular remodeling through AT2 receptor expression and signaling

2000 ◽  
Vol 2 (1) ◽  
pp. 13-20 ◽  
Author(s):  
MASAHIRO AKISHITA ◽  
MASATSUGU HORIUCHI ◽  
HIROYUKI YAMADA ◽  
LUNAN ZHANG ◽  
GOTARO SHIRAKAMI ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Remodeling ◽  
Muscle Growth ◽  
Vascular Diseases ◽  
Lesion Size ◽  
Receptor Expression ◽  
Growth Inhibitory ◽  
Interferon Regulatory Factor 1

Akishita, Masahiro, Masatsugu Horiuchi, Hiroyuki Yamada, Lunan Zhang, Gotaro Shirakami, Kouichi Tamura, Yasuyoshi Ouchi, and Victor J. Dzau. Inflammation influences vascular remodeling through AT2 receptor expression and signaling. Physiol. Genomics 2: 13–20, 2000.—The AT2 receptor, which exerts growth inhibitory effects in cell culture, is present scantily in the adult vasculature but is reexpressed after vascular injury. To examine the in vivo role of this receptor in vascular diseases, we developed a mouse model of vascular remodeling and compared the responses in wild-type ( Agtr2+) and AT2 receptor knockout ( Agtr2−) mice. Polyethylene cuff placement on the femoral artery led to the vascular expression of cytokines, the transcriptional factor interferon regulatory factor-1 (IRF-1), and both the AT1 and AT2 receptors. Although the expressions of IRF-1 and AT1 receptor were induced to comparable levels in both the Agtr2+ and Agtr2− mice, the neointimal lesion size and the smooth muscle cell proliferation were twice greater in the Agtr2− than in the Agtr2+ mouse. Correlated with this difference, AT2 receptor expression was induced predominantly in the smooth muscle cells of Agtr2+ mouse. These results demonstrate that the AT2 receptor plays an important role in nonocclusive inflammatory injury by mediating the effects of inflammation on vascular smooth muscle growth inhibition.

scholarly journals Cilostazol inhibits uremic toxin–induced vascular smooth muscle cell dysfunction: role of Axl signaling

2017 ◽  
Vol 312 (3) ◽  
pp. F398-F406 ◽  
Author(s):  
Chien-Hsing Lee ◽  
Yi-Jen Hung ◽  
Yi-Shing Shieh ◽  
Chu-Yen Chien ◽  
Yu-Juei Hsu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Uremic Toxin ◽  
Cell Functions

Chronic kidney disease (CKD) is associated with increased cardiovascular mortality, and vascular smooth muscle cell (VSMC) dysfunction plays a pivotal role in uremic atherosclerosis. Axl signaling is involved in vascular injury and is highly expressed in VSMCs. Recent reports have shown that cilostazol, a phosphodiesterase type 3 inhibitor (PDE3), can regulate various stages of the atherosclerotic process. However, the role of cilostazol in uremic vasculopathy remains unclear. This study aimed to identify the effect of cilostazol in VSMCs in the experimental CKD and to investigate whether the regulatory mechanism occurs through Axl signaling. We investigated the effect of P-cresol and cilostazol on Axl signaling in A7r5 rat VSMCs and the rat and human CKD models. From the in vivo CKD rats and patients, aortic tissue exhibited significantly decreased Axl expression after cilostazol treatment. P-cresol increased Axl, proliferating of cell nuclear antigen (PCNA), focal adhesion kinase (FAK), and matrix metalloproteinase-2 (MMP-2) expressions, decreased caspase-3 expression, and was accompanied by increased cell viability and migration. Cilostazol significantly reversed P-cresol-induced Axl, downstream gene expressions, and cell functions. Along with the increased Axl expression, P-cresol activated PLCγ, Akt, and ERK phosphorylation and cilostazol significantly suppressed the effect of P-cresol. Axl knockdown significantly reversed the expressions of P-cresol-induced Axl-related gene expression and cell functions. Cilostazol with Axl knockdown have additive changes in downstream gene expression and cell functions in P-cresol culture. Both in vitro and in vivo experimental CKD models elucidate a new signal transduction of cilostazol-mediated protection against uremic toxin-related VSMCs dysfunction and highlight the involvement of the Axl signaling and downstream pathways.

scholarly journals Rheology of airway smooth muscle cells is associated with cytoskeletal contractile stress

2004 ◽  
Vol 96 (5) ◽  
pp. 1600-1605 ◽  
Author(s):  
Dimitrije Stamenović ◽  
Béla Suki ◽  
Ben Fabry ◽  
Ning Wang ◽  
Jeffrey J. Fredberg ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Rheological Properties ◽  
Airway Smooth Muscle ◽  
Muscle Cells ◽  
Airway Smooth Muscle Cells ◽  
Cell Functions ◽  
Contractile Stress ◽  
Reported Data

Recently reported data from mechanical measurements of cultured airway smooth muscle cells show that stiffness of the cytoskeletal matrix is determined by the extent of static contractile stress borne by the cytoskeleton (Wang N, Tolić-Nørrelykke IM, Chen J, Mijailovich SM, Butler JP, Fredberg JJ, and Stamenović D. Am J Physiol Cell Physiol 282, C606-C616, 2002). On the other hand, rheological measurements on these cells show that cytoskeletal stiffness changes with frequency of imposed mechanical loading according to a power law (Fabry B, Maksym GN, Butler JP, Glogauer M, Navajas DF, and Fredberg JJ. Phys Rev Lett 87: 148102, 2001). In this study, we examine the possibility that these two empirical observations might be interrelated. We combine previously reported data for contractile stress of human airway smooth muscle cells with new data describing rheological properties of these cells and derive quantitative, mathematically tractable, and experimentally verifiable empirical relationships between contractile stress and indexes of cell rheology. These findings reveal an intriguing role of the contractile stress: although it maintains structural stability of the cell under applied mechanical loads, it may also regulate rheological properties of the cytoskeleton, which are essential for other cell functions.

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