Substance P (NK1) receptor immunoreactivity on endothelial cells of the rat tracheal mucosa

1996 ◽  
Vol 270 (3) ◽  
pp. L404-L414 ◽  
Author(s):  
J. J. Bowden ◽  
P. Baluk ◽  
P. M. Lefevre ◽  
S. R. Vigna ◽  
D. M. McDonald
Keyword(s):  
Endothelial Cells ◽  
Substance P ◽  
Direct Action ◽  
Sensory Nerve ◽  
Nerve Fibers ◽  
Receptor Internalization ◽  
Nk1 Receptor ◽  
Tracheal Mucosa ◽  
Nk1 Receptors ◽  
Plasma Leakage

Substance P released from sensory nerve fibers causes plasma leakage through an action on neurokinin-1 (NK1 or substance P) receptors. However, it is unknown whether the leakage results from a direct action of substance P on endothelial cells. We determined the distribution of NK1 receptors at sites of plasma leakage in the rat tracheal mucosa, using NK1 receptor-immunoreactive endosomes as markers of substance P-induced receptor internalization. We found that immunoreactive endosomes were located in the endothelial cells of venules and capillaries but not in those of arterioles. Five minutes after vagal stimulation for 1 min, the number of immunoreactive endosomes in endothelial cells was increased 5-fold in postcapillary venules (mean of 17.4 endosomes/100 micron2 compared with a baseline value of 3.4), 15-fold in collecting venules (12.1 compared with 0.8), and 4-fold in capillaries (2.5 compared with 0.7). No endosomes were found in arterioles under either condition. The number of immunoreactive endosomes in individual vessels corresponded to the amount of stimulus-induced plasma leakage. Both the receptor internalization and the plasma leakage were blocked by the selective NK1 receptor antagonist SR-140333 (100 microgram/kg iv). Although both substance P (5 microgram/kg iv) and platelet-activating factor (5 microgram/kg iv) caused plasma leakage, only substance P induced receptor internalization. We conclude that substance P, released from sensory nerve fibers, causes plasma leakage through a direct action on endothelial cells of venules, and that this action is followed by the internalization of NK1 receptors into endosomes.

Upregulation of substance P receptors in angiogenesis associated with chronic airway inflammation in rats

1997 ◽  
Vol 273 (3) ◽  
pp. L565-L571 ◽  
Author(s):  
P. Baluk ◽  
J. J. Bowden ◽  
P. M. Lefevre ◽  
D. M. McDonald
Keyword(s):  
Endothelial Cells ◽  
Substance P ◽  
Blood Vessels ◽  
Sensory Nerves ◽  
Mycoplasma Pulmonis ◽  
Tracheal Mucosa ◽  
Fischer 344 ◽  
Nk1 Receptors ◽  
Plasma Leakage ◽  
Neurokinin 1

In rat airways, substance P released from sensory nerves induces plasma leakage via neurokinin-1 (NK1) receptors on endothelial cells. In pathogen-free rats, both leakage and endothelial NK1 receptors are most abundant in postcapillary venules. In Mycoplasma pulmonis-infected rats, extensive angiogenesis occurs in the tracheal mucosa. The capillary-sized (< 10 microns in diameter) angiogenic blood vessels are abnormally sensitive to substance P. The aim of this study was to determine whether increased expression of NK1 receptors contributes to this abnormal sensitivity. Fischer 344 rats were infected with M. pulmonis and were challenged with substance P (5 micrograms/kg i.v.), and then plasma leakage in the tracheal mucosa was measured by extravasation of Monastral blue (30 mg/kg i.v.). NK1 receptors on endothelial cells were localized by immunohistochemistry. Five minutes after substance P, NK1 receptor-immunoreactive endosomes were five times more abundant in endothelial cells of angiogenic capillaries in M. pulmonis-infected rats than in corresponding capillaries in pathogen-free controls (17.1 +/- 2.3 vs. 3.5 +/- 0.4 endosomes/100 micron 2 of endothelial surface). Endosomes were slightly more abundant in postcapillary venules 15-35 microns in diameter in infected rats (23.0 +/- 0.6 vs. 19.2 +/- 0.7 endosomes/100 micron 2). Similarly, after substance P, angiogenic capillaries had much more Monastral blue labeling (area density: 18.8 +/- 1.5 vs. 2.9 +/- 0.5% of vessel wall), whereas postcapillary venules had about the same amount of labeling (36.0 +/- 3.7 vs. 34.1 +/- 1.8%). We conclude that increased expression of NK1 receptors, which are internalized into endosomes after ligand binding, contributes to the abnormal sensitivity of endothelial cells of angiogenic blood vessels to substance P in the airways of M. pulmonis-infected rats.

NK1 receptors mediate leukocyte adhesion in neurogenic inflammation in the rat trachea

1995 ◽  
Vol 268 (2) ◽  
pp. L263-L269 ◽  
Author(s):  
P. Baluk ◽  
C. Bertrand ◽  
P. Geppetti ◽  
D. M. McDonald ◽  
J. A. Nadel
Keyword(s):  
Substance P ◽  
Hypertonic Saline ◽  
Receptor Agonist ◽  
Neurogenic Inflammation ◽  
Leukocyte Adhesion ◽  
Neurokinin A ◽  
Plasma Extravasation ◽  
Nk1 Receptor ◽  
Nk1 Receptors ◽  
Plasma Leakage

In neurogenic inflammation, tachykinins trigger the adhesion of neutrophils and eosinophils to leaky venules. The goals of the present study were to determine whether this leukocyte adhesion is mediated by neurokinin type 1 (NK1) receptors and to determine whether the amount of leukocyte adhesion corresponds to the amount of plasma leakage. Anesthetized rats were injected intravenously with substance P, the NK1 receptor agonist [Sar9, Met(O2)11]-substance P, or the NK2 receptor agonist [beta-Ala8]neurokinin A-(4–10). Five minutes later, the adherent neutrophils and eosinophils in blood vessels of the tracheal mucosa were stained histochemically and plasma leakage was quantified, as assessed by the extravasation of Monastral blue. Substance P and the NK1 agonist caused similar amounts of leukocyte adhesion, but the NK2 agonist had no effect. Pretreatment with the NK1 receptor antagonist CP-96,345 (4 mg/kg iv), before challenge with substance P, capsaicin, or aerosol hypertonic saline, reduced the amount of neutrophil adhesion by 56%, 93%, and 57% and reduced the amount of eosinophil adhesion by 70%, 83%, and 65%, respectively. Plasma extravasation was decreased by 89%, 95%, and 94%. The number of adherent neutrophils in the trachea was strongly correlated with the number of adherent eosinophils (r2 = 0.61). The greatest amount of leukocyte adhesion occurred in larger diameter venules than did the maximal amount of Monastral blue leakage. We conclude that NK1 receptors mediate the adhesion of neutrophils and eosinophils as well as the plasma leakage triggered by substance P, capsaicin, or hypertonic saline. This leukocyte adhesion evidently does not occur at exactly the same sites as the plasma leakage.

scholarly journals Substance P and Alpha-Calcitonin Gene-Related Peptide Differentially Affect Human Osteoarthritic and Healthy Chondrocytes

2021 ◽  
Vol 12 ◽  
Author(s):  
Sabine Stöckl ◽  
Annett Eitner ◽  
Richard J. Bauer ◽  
Matthias König ◽  
Brian Johnstone ◽  
...  
Keyword(s):  
Substance P ◽  
Structural Damage ◽  
Articular Chondrocytes ◽  
Sensory Nerve ◽  
Calcitonin Gene Related Peptide ◽  
Nerve Fibers ◽  
Joint Disease ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Oa Chondrocytes

Osteoarthritis (OA) is a degenerative joint disease that not only causes cartilage loss but also structural damage in all joint tissues. Joints are innervated by alpha-calcitonin gene-related peptide (αCGRP) and substance P (SP)-positive sensory nerve fibers. Alteration of sensory joint innervation could be partly responsible for degenerative changes in joints that contribute to the development of OA. Therefore, our aim was to analyze and compare the molecular effects of SP and αCGRP on the metabolism of articular chondrocytes from OA patients and non-OA cartilage donors. We treated the cells with SP or αCGRP and analysed the influence of these neuropeptides on chondrocyte metabolism and modulation of signaling pathways. In chondrocytes from healthy cartilage, SP had minimal effects compared with its effects on OA chondrocytes, where it induced inflammatory mediators, inhibited chondrogenic markers and promoted apoptosis and senescence. Treatment with αCGRP also increased apoptosis and senescence and reduced chondrogenic marker expression in OA chondrocytes, but stimulated an anabolic and protective response in healthy chondrocytes. The catabolic influence of SP and αCGRP might be due to activation of ERK signaling that could be counteracted by an increased cAMP response. We suggest that a switch between the G-subunits of the corresponding receptors after binding their ligands SP or αCGRP plays a central role in mediating the observed effects of sensory neuropeptides on chondrocytes.

Sensory denervation by neonatal capsaicin treatment exacerbates Mycoplasma pulmonis infection in rat airways

1996 ◽  
Vol 270 (3) ◽  
pp. L393-L403 ◽  
Author(s):  
J. J. Bowden ◽  
P. Baluk ◽  
P. M. Lefevre ◽  
T. R. Schoeb ◽  
J. R. Lindsey ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Chronic Inflammation ◽  
Fold Increase ◽  
Nerve Fibers ◽  
Sensory Nerves ◽  
Mycoplasma Pulmonis ◽  
Tracheal Mucosa ◽  
Airway Mucosa ◽  
Plasma Leakage ◽  
Mucosal Thickening

Mycoplasma pulmonis infection in rats results in life-long disease, characterized by chronic inflammation of the airway mucosa with widespread accumulation of lymphoid tissue, mucous cell hyperplasia, and mucosal thickening. In addition, there is angiogenesis and increased sensitivity of mucosal blood vessels to substance P (SP), so tachykinins released from sensory nerve fibers cause an abnormally large amount of plasma leakage. We sought to learn whether the sensory nerves influence the severity of the chronic inflammatory response of M. pulmonis infection. Our strategy was to destroy the nerves by capsaicin pretreatment at birth, infect the rats with M. pulmonis at 8 wk of age, and then study the animals 6 wk later. We found that capsaicin pretreatment increased the severity of the infection, exaggerated the pathological changes in the tracheal mucosa, and increased the amount of SP-induced plasma leakage, as quantified with Monastral blue. The thickness of the tracheal mucosa in these infected rats was 80% greater than in their vehicle-pretreated counterparts and 200% greater than in the pathogen-free controls. The area density of Monastral blue-labeled blood vessels averaged 20% in the infected rats pretreated with capsaicin, which represented a 40-fold increase over the leakage in the pathogen-free group. By comparison, the amount of Monastral blue labeling was only 13% in rats pretreated with vehicle (P<0.05), which was a 22-fold increase over the corresponding pathogen-free group. The number of SP-immunoreactive nerve fibers was reduced both by neonatal capsaicin and by infection (87 and 63% reductions, respectively); but when the two conditions were combined, their effects were not additive (79% reduction), perhaps because of nerve regrowth. We conclude that destruction of sensory nerves increases the severity of infection- induced chronic inflammation in the airway mucosa, with exaggerated mucosal thickening, angiogenesis, plasma leakage, and nerve remodeling.

scholarly journals Airway vasculature after mycoplasma infection: chronic leakiness and selective hypersensitivity to substance P

2001 ◽  
Vol 280 (2) ◽  
pp. L286-L297 ◽  
Author(s):  
Marilyn L. Kwan ◽  
Antonio D. Gómez ◽  
Peter Baluk ◽  
Hiroya Hashizume ◽  
Donald M. McDonald
Keyword(s):  
Substance P ◽  
Adrenergic Receptor ◽  
Platelet Activating Factor ◽  
Mycoplasma Pulmonis ◽  
Tracheal Mucosa ◽  
Vessel Remodeling ◽  
Microvascular Remodeling ◽  
Plasma Leakage ◽  
Endothelial Gaps ◽  
Adrenergic Receptor Agonist

Angiogenesis and microvascular remodeling are features of chronic airway inflammation caused by Mycoplasma pulmonis infection in rats. As airway blood vessels undergo remodeling, they become unusually sensitive to substance P-induced plasma leakage. Here we determined whether the remodeled vessels are leaky under baseline conditions, whether their heightened sensitivity is specific to substance P, and whether the leakage is reversible. Four weeks after infection, the amount of baseline leakage of Evans blue in the tracheal mucosa was two to five times the normal level. Gaps < 1 μm in diameter were located between endothelial cells in some remodeled vessels. Substance P, but not platelet-activating factor or 5-hydroxytryptamine, produced an exaggerated leakage response. Inhalation of the β2-adrenergic receptor agonist salmeterol reduced the leakage by <60%. We conclude that the blood vessel remodeling after M. pulmonis infection is associated with microvascular leakiness due, in part, to the formation of endothelial gaps. This leakage is accompanied by an abnormal sensitivity to substance P but not to platelet-activating factor or 5-hydroxytryptamine and can be reduced by β2-agonists.

NK1 receptors mediate neurogenic inflammatory increase in blood flow in rat airways

1993 ◽  
Vol 74 (5) ◽  
pp. 2462-2468 ◽  
Author(s):  
G. Piedimonte ◽  
J. I. Hoffman ◽  
W. K. Husseini ◽  
R. M. Snider ◽  
M. C. Desai ◽  
...  
Keyword(s):  
Blood Flow ◽  
Substance P ◽  
Neurogenic Inflammation ◽  
Sensory Nerves ◽  
Nk1 Receptor ◽  
Nk1 Receptors ◽  
Calcitonin Gene ◽  
Nk1 Receptor Antagonist ◽  
Selective Agonists ◽  
Neurokinin 1

We studied the effect of neurogenic inflammation on airway blood flow in anesthetized F-344 rats. Three successive determinations of blood flow were made by injecting radionuclide-labeled microspheres suspended in 70% dextrose into the left ventricle. A selective agonist of the tachykinin receptor neurokinin 1 (NK1) increased airway blood flow, but NK2- and NK3-selective agonists were without effect. The natural agonist of NK1 receptors, substance P (1 micrograms/kg), increased airway blood flow, an effect that was abolished by the selective NK1 receptor antagonist CP-99,994 [(+)-(2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine] but not by the (2R,3R)-enantiomer CP-100,263. Capsaicin (25 micrograms/kg), a drug that releases tachykinins and calcitonin gene-related peptide from sensory nerves, increased airway blood flow, and again this effect was abolished by CP-99,994. We also studied the effect of a selective inhibitor (captopril, 2.5 mg/kg) of the tachykinin-degrading enzyme kininase II [or angiotensin-converting enzyme (ACE)] on substance P-induced airway vasodilation. Captopril potentiated and prolonged the vasodilator effect of substance P. We conclude that neurogenic vasodilation in rat airways is due to the release of substance P, acts via NK1 receptors, and may be modulated by ACE.

scholarly journals Co-localization of the vanilloid capsaicin receptor and substance P in sensory nerve fibers innervating cochlear and vertebro-basilar arteries

Neuroscience ◽  
2004 ◽  
Vol 124 (4) ◽  
pp. 919-927 ◽  
Author(s):  
Z Vass ◽  
C.F Dai ◽  
P.S Steyger ◽  
G Jancsó ◽  
D.R Trune ◽  
...  
Keyword(s):  
Substance P ◽  
Sensory Nerve ◽  
Nerve Fibers ◽  
Capsaicin Receptor ◽  
Basilar Arteries

The beta 2-adrenergic receptor agonist formoterol reduces microvascular leakage by inhibiting endothelial gap formation

1994 ◽  
Vol 266 (4) ◽  
pp. L461-L468 ◽  
Author(s):  
P. Baluk ◽  
D. M. McDonald
Keyword(s):  
Endothelial Cells ◽  
Substance P ◽  
Vascular Permeability ◽  
Evans Blue ◽  
Adrenergic Receptor ◽  
Gap Formation ◽  
Plasma Leakage ◽  
Beta 2 ◽  
Endothelial Gaps

beta 2-Adrenergic receptor agonists inhibit the increase in vascular permeability produced by a variety of inflammatory mediators. The anti-edema effect of beta 2-agonists is assumed to result from a direct action on endothelial cells, but such a mechanism has not been demonstrated in vivo. The aim of this study was to determine whether beta 2-agonists exert their anti-edema effect by inhibiting the formation of endothelial gaps at sites of plasma leakage. Vascular permeability in the rat trachea was increased by electrical stimulation of the vagus nerve or by intravenous injection of substance P (5 micrograms/kg iv). Plasma leakage was quantified by using Monastral blue and Evans blue as tracers. Endothelial gaps were made visible for light microscopy by staining the borders of endothelial cells with silver nitrate. The experiments showed that the selective beta 2-agonist formoterol, which is known to have anti-edema effects, reduced the plasma leakage produced by either stimulus. The effect was dose dependent, with a formoterol dose of 10 micrograms/kg iv producing maximal reduction of Monastral blue leakage (64 +/- 14%). The amounts of extravasation of Monastral blue and Evans blue were closely correlated (r2 = 0.76, P < 0.01). After the injection of substance P, there were 15.3 +/- 1.0 gaps/endothelial cells in postcapillary venules of vehicle-pretreated rats, but only 5.0 +/- 0.2 gaps/cell in formoterol-pretreated (10 micrograms/kg iv) rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Sensory Nerve Endings in the Mucosa of the Epiglottis—Morphologic Investigations with Silver Impregnation, Immunohistochemistry, and Electron Microscopy

1987 ◽  
Vol 96 (1) ◽  
pp. 55-62 ◽  
Author(s):  
Takemoto Shin ◽  
Shun Watanabe ◽  
Shigeru Wada ◽  
Tadatsugu Maeyama
Keyword(s):  
Electron Microscopy ◽  
Substance P ◽  
Sensory Nerve ◽  
Nerve Fibers ◽  
Silver Impregnation ◽  
Taste Bud ◽  
Nerve Endings ◽  
Electron Microscopic ◽  
Sensory Nerve Endings ◽  
Microscopic Studies

This study was conducted in order to investigate the structure of sensory nerve endings of the human epiglottis and substance P immunoreactive nerve fibers of the canine epiglottis in relationship to physiologic functions of the larynx. The human epiglottis was observed by light microscopy (silver impregnation) and electron microscopy, and the canine epiglottis was studied by peroxidase-anti-peroxidase (PAP) immunohistochemistry. The results are summarized as follows: (1) In the membranes of the epiglottis, we observed free endings of simple or complex tree shape, corpuscle endings with glomerular patterns, and taste-bud-like structures, and (2) electron microscopic studies revealed varicosity of the terminal axon with processes that contained small, clear and large, dense cored vesicles. Substance P was observed in these structures, and it was suggested that substance P was related to perception in the larynx.

scholarly journals Susbstance P Levels in Children with Atopic Dermatitis

2021 ◽  
Vol 33 (3) ◽  
pp. 182
Author(s):  
Khairina Nasution ◽  
Deryne Anggia Paramita ◽  
Nova Zairina Lubis
Keyword(s):  
Atopic Dermatitis ◽  
Substance P ◽  
Observational Study ◽  
Sensory Nerve ◽  
Skin Inflammation ◽  
Nerve Fibers ◽  
Cross Sectional ◽  
Adolescent Group ◽  
Group 12 ◽  
Common Skin

Background: Atopic dermatitis (AD) is the most common skin disease in infants and children. AD is influenced by hereditary and environmental factors, and it is characterized by an inflammatory reaction in the skin. In developing countries, children suffering from AD are estimated around 10–20%, of which 60% of the cases persist into adulthood. Substance P is a cutaneous neuropeptide that contributes to the pathogenesis of AD. Substance P promotes the production of nerve growth factors from keratinocytes, and the release of histamine, leukotriene, or tumor necrosis factor from mast cells, which cause the growth of sensory nerve fibers, augmentation of skin inflammation, and are considered pruritogenic factors. Purpose: This study aims to determine the description of substance P in children with atopic dermatitis using a descriptive observational study with a cross-sectional approach. Methods: This is a destructive observational study with a crossectional approach samples were selected from AD patients at the Universitas Sumatera Utara Hospital. Result: The largest group of subjects were childhood (2–12 years old), there was 60%, followed by the adolescent group (12–18 years old) and the infant group (<2 years old). In the childhood group, the highest level of substance P was found in girls with a mean of 349.03 ± 146.7. On the other hand, the highest levels of substance P in the adolescent were found in males with a mean of 243.73 ± 64.57 ng/L. Conclusion: In this study, we found that the level of substance p was higher in the childhood group.

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