Substance P (NK1)- and neurokinin A (NK2)-receptor gene expression in inflammatory airway diseases

1995 ◽  
Vol 269 (3) ◽  
pp. L309-L317 ◽  
Author(s):  
T. R. Bai ◽  
D. Zhou ◽  
T. Weir ◽  
B. Walker ◽  
R. Hegele ◽  
...  
Keyword(s):  
Substance P ◽  
Mrna Expression ◽  
Airflow Obstruction ◽  
Ribonuclease Protection Assay ◽  
Neurokinin A ◽  
Mrna Levels ◽  
Nk1 Receptor ◽  
Receptor Mrna ◽  
Nk3 Receptor ◽  
Nk2 Receptor

The tachykinin neuropeptides substance P and neurokinin (NK) A have been postulated to participate in the inflammatory reaction in airways of smokers and asthmatics. We have examined the hypothesis that the expression of one or more of the three cloned tachykinin receptors (NK1, NK2, and NK3) is increased in inflammatory airway disorders, which could result in augmentation of the effect of released tachykinin neuropeptides. NK1 receptor and NK2 receptor but not NK3-receptor mRNA were detected by ribonuclease protection assay in RNA from both cartilaginous and membranous bronchi and subpleural lung. In lung samples containing membranous airways, NK2-receptor mRNA expression was increased fourfold in asthmatics compared with nonsmoking controls, whereas NK1-receptor mRNA levels were similar in the two groups. NK1- and NK2-receptor mRNA expression was increased twofold in smokers without airflow obstruction compared with nonsmokers, whereas NK1-receptor mRNA expression was significantly lower in patients with chronic obstructive pulmonary disease compared with smoking controls. In situ hybridization indicated NK1-receptor mRNA was expressed in submucosal glands and airway epithelial cells, whereas NK2-receptor and NK3-receptor mRNA were not detected. These observations have implications for the pathophysiology and treatment of both asthma and tobacco smoke-induced airway inflammation.

scholarly journals Primary structure and receptor-binding properties of a neurokinin A-related peptide from frog gut

1992 ◽  
Vol 287 (3) ◽  
pp. 827-832 ◽  
Author(s):  
Y Wang ◽  
T Badgery-Parker ◽  
S Lovas ◽  
N Chartrel ◽  
H Vaudry ◽  
...  
Keyword(s):  
Substance P ◽  
Primary Structure ◽  
Rat Tissues ◽  
Neurokinin A ◽  
Related Peptide ◽  
Nk3 Receptor ◽  
Stomach Fundus ◽  
Nk2 Receptor ◽  
Rat Submandibular Gland ◽  
Isoleucine Residue

A tachykinin peptide was isolated from an extract of the intestine of the European green frog, Rana ridibunda, and its primary structure was established as: His-Lys-Leu-Asp-Ser-Phe-Ile-Gly-Leu-Met.CONH2. This sequence was confirmed by chemical synthesis and shows two amino acid substitutions (leucine for threonine at position 3 and isoleucine for valine at position 7) compared with neurokinin A. Binding parameters for synthetic [Leu3, Ile7]neurokinin A and mammalian tachykinins were compared using receptor-selective radioligands and crude membranes from tissues enriched in the NK1, NK2 and NK3 receptors. [Leu3, Ile7]Neurokinin A was approx. 3-fold less potent than substance P in inhibiting the binding of 125I-labelled [Sar9, Met(O2)11]substance P (labelled with Bolton-Hunter reagent) to rat submandibular gland (NK1 receptor), 8-fold less potent than neurokinin A in inhibiting the binding of [2-[125I]iodohistidine1]neurokinin A to rat stomach fundus (NK2 receptor) and 6-fold less potent than neurokinin B in inhibiting the binding of 125I-Bolton-Hunter-labelled scyliorhinin II to rat brain (NK3 receptor). Thus the frog neurokinin A-related peptide shows moderate affinity but lack of selectivity for all three tachykinin-binding sites in rat tissues. This non-selectivity is similar to that displayed by the molluscan tachykinin, eledoisin, which also contains an isoleucine residue in the corresponding position in the molecule.

A novel motility effect of tachykinins in normal and inflamed colon

1997 ◽  
Vol 272 (6) ◽  
pp. G1607-G1614 ◽  
Author(s):  
M. Tsukamoto ◽  
S. K. Sarna ◽  
R. E. Condon
Keyword(s):  
Substance P ◽  
Receptor Agonist ◽  
Contractile Response ◽  
Contractile Activity ◽  
Nk1 Receptor ◽  
Receptor Antagonists ◽  
Nk3 Receptor ◽  
Nk2 Receptor ◽  
Higher Doses ◽  
Stimulation Of

The role of tachykinins in stimulating phasic and giant migrating contractions (GMCs) in the normal and inflamed colon in conscious dogs was investigated by close-intra-arterial infusions of test substances. At low doses (0.1 nmol), substance P and neurokinin (NK1) receptor agonist ([Sar9,Met(O2)11]substance P] stimulated phasic contractions only. At higher doses (2.0 nmol), they stimulated phasic contractions and GMCs. The phasic contractions were blocked partially but significantly by prior close-intra-arterial infusions of tetrodotoxin and atropine but not by hexamethonium. NK1 receptor antagonist partially but significantly inhibited the phasic contractile response to substance P, whereas NK2 and NK3 receptor antagonists had no significant effect. The contractile response to NK2 receptor agonist was less than one-half of the response to substance P; NK3 receptor agonist did not stimulate any contractile activity. The stimulation of GMCs by higher doses of substance P was not blocked by prior infusions of atropine, tetrodotoxin, or NK1, NK2, and NK3 receptor antagonists, nor was the contractile response to substance P blocked by H1 and H2 receptor antagonists. Inflammation depressed the phasic contractile response but enhanced the stimulation of GMCs by substance P. The ability of substance P to stimulate GMCs is novel and suggests its potential role in increasing the frequency of these contractions during colonic inflammation.

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.

Expression of Substance P (NK1) Receptor mRNA in Human Nose

1998 ◽  
Vol 118 (5) ◽  
pp. 717-722 ◽  
Author(s):  
Hideaki Shirasaki, Kohji Asakura, S
Keyword(s):  
Substance P ◽  
Nk1 Receptor ◽  
Receptor Mrna ◽  
Human Nose

Substance P-induced histamine release in tracheally perfused guinea pig lungs

1995 ◽  
Vol 78 (4) ◽  
pp. 1234-1241 ◽  
Author(s):  
C. M. Lilly ◽  
A. E. Hall ◽  
I. W. Rodger ◽  
L. Kobzik ◽  
K. J. Haley ◽  
...  
Keyword(s):  
Mast Cells ◽  
Substance P ◽  
Guinea Pig ◽  
Histamine Release ◽  
Receptor Activation ◽  
Neurokinin A ◽  
Histamine Liberation ◽  
Nk1 Antagonist ◽  
Nk2 Receptor ◽  
Receptor Agonists And Antagonists

The capacity of substance P (SP) and endogenously released tachykinins to liberate histamine was examined in isolated tracheally perfused guinea pig lungs. Increasing doses of tracheally injected SP were associated with the recovery of increasing amounts of histamine from lung effluent. The mechanism of SP-induced histamine liberation was explored in studies with neurokinin-(NK) receptor agonists and antagonists. Tracheal injection of either the NK1 agonist [Sar9,Met(O2)11]SP or the NK2 agonist [beta-Ala8]-neurokinin A-(4–10) was associated with a significant increase in histamine recovery from lung effluent. In addition, both the NK1 antagonist CP-99994 and the NK2 antagonist SR-48968 significantly inhibited SP-induced histamine release. These findings support the hypothesis that SP can liberate histamine from guinea pigs lungs by a mechanism that depends predominantly on NK1- and NK2-receptor activation. The liberation of endogenous tachykinins by acute tracheal injection of capsaicin was also associated with augmented histamine recovery, which was inhibited by combined NK1- and NK2-receptor blockade. Tracheal injection of SP was associated with an increase in the percentage of airway mast cells exhibiting histological evidence of degranulation. This study demonstrates that exogenous SP, as well as endogenous tachykinins released from capsaicin-sensitive neurons, can liberate histamine, most likely from airway mast cells, by a mechanism that depends predominantly on the activation of NK1 and NK2 receptors.

scholarly journals Expression of Tachykinins and Tachykinin Receptors and Interaction with Kisspeptin in Human Granulosa and Cumulus Cells1

2016 ◽  
Vol 94 (6) ◽  
Author(s):  
Jordán García-Ortega ◽  
Francisco M. Pinto ◽  
Nicolás Prados ◽  
Aixa R. Bello ◽  
Teresa A. Almeida ◽  
...  
Keyword(s):  
Cell Function ◽  
Oocyte Retrieval ◽  
Cumulus Cells ◽  
Mrna Levels ◽  
Human Ovary ◽  
Rt Pcr ◽  
Protein Levels ◽  
Preovulatory Follicles ◽  
Nk3 Receptor ◽  
Nk2 Receptor

Abstract The neurokinin B/NK3 receptor (NK3R) and kisspeptin/kisspeptin receptor (KISS1R), two systems which are essential for reproduction, are coexpressed in human mural granulosa (MGC) and cumulus cells (CCs). However, little is known about the presence of other members of the tachykinin family in the human ovary. In the present study, we analyzed the expression of substance P (SP), hemokinin-1 (HK-1), NK1 receptor (NK1R), and NK2 receptor (NK2R) in MGCs and CCs collected from preovulatory follicles of oocyte donors at the time of oocyte retrieval. RT-PCR, quantitative RT-PCR, immunocytochemistry, and Western blotting were used to investigate the patterns of expression of tachykinin and tachykinin receptor mRNAs and proteins and the possible interaction between the tachykinin family and kisspeptin. Intracellular free Ca2+ levels ([Ca2+]i) in MGCs after exposure to SP or kisspeptin in the presence of SP were also measured. We found that SP, HK-1, the truncated NK1R isoform NK1R-Tr, and NK2R were all expressed in MGCs and CCs. NK1R-Tr mRNA and NK2R mRNA and protein levels were higher in MGCs than in CCs from the same patients. Treatment of cells with kisspeptin modulated the expression of HK-1, NK3R, and KISS1R mRNAs, whereas treatment with SP regulated kisspeptin mRNA levels and reduced the [Ca2+]i response produced by kisspeptin. These data demonstrate that the whole tachykinin system is expressed and acts in coordination with kisspeptin to regulate granulosa cell function in the human ovary.

scholarly journals Increased endothelin and endothelin receptor mRNA expression in polycystic kidneys of cpk mice.

1993 ◽  
Vol 4 (4) ◽  
pp. 1064-1072 ◽  
Author(s):  
T Nakamura ◽  
I Ebihara ◽  
M Fukui ◽  
S Osada ◽  
Y Tomino ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Transforming Growth Factor Beta ◽  
Proliferating Cell Nuclear Antigen ◽  
Transforming Growth Factor ◽  
Nuclear Antigen ◽  
Tnf Alpha ◽  
Mrna Levels ◽  
Tgf Beta ◽  
Receptor Mrna ◽  
Proliferating Cell

The renal mRNA levels of endothelin (ET)-1 and ET-3 and for ET receptors A and B were measured in the cystic kidneys of cpk/cpk mice at 1, 2, and 3 wk of age. At 1 wk of age, renal ET-1 mRNA was 3.2-fold greater in cystic mice than in controls and continued to increase with the progression of cyst formation to reach 10.4-fold more than controls at 3 wk. ET-3 mRNA levels did not differ between cystic and control mice. Renal ETA and ETB receptor mRNA increased gradually in cystic mice with the progression of their cysts, reaching 4.2- and 6.3-fold increases over controls, respectively, at 3 wk. Proliferating cell nuclear antigen mRNA expression was also examined, and proliferating cell nuclear antigen mRNA levels were found to be significantly increased in the kidneys of cystic mice compared with controls: 2. 1-fold at 1 wk, 4.5-fold at 2 wk, and 7.8-fold at 3 wk. The mRNA levels for transforming growth factor beta (TGF-beta) and tumor necrosis factor alpha (TNF-alpha) in the kidneys of cystic mice were also examined and were found to be increased progressively with age (TGF-beta, 2.1-fold at 1 wk, 4.2-fold at 2 wk, and 6.2-fold at 3 wk; TNF-alpha, 2.2-fold at 1 wk, 3.8-fold at 2 wk, and 5.4-fold at 3 wk).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Distribution of Neurokinin 2 and 3 Receptor mRNA In the Normal Equine Gastrointestinal Tract and Effect of Inflammation on Neurokinin 1, 2, And 3 Receptor mRNA In the Equine Jejunum.

2020 ◽  
pp. 1-13
Keyword(s):  
Mrna Expression ◽  
Intestinal Tract ◽  
Ischemia Reperfusion ◽  
The Body ◽  
Sham Operation ◽  
Receptor Mrna ◽  
Neurokinin Receptor ◽  
Significant Difference ◽  
Nk2 Receptor ◽  
Neurokinin 1

Abstract Objectives – To quantify neurokinin 2 and 3 receptor mRNA from nine regions throughout the equine intestinal tract, and to evaluate the effect of jejunal ischemia/reperfusion and intraluminal obstruction on neurokinin 1, 2, and 3 receptor mRNA. Methods – Specimens were harvested from 5 adult horses euthanized for reasons unrelated to gastrointestinal disease for the study of normal distribution of neurokinin receptor mRNA. Jejunal segments from 6 healthy adult horses subjected to intraluminal distension or ischemia/reperfusion injury were harvested to study the influence of inflammation on neurokinin 1, 2, and 3 receptor mRNA expression. RNA was isolated from normal tissues and also from tissues that underwent either a sham operation (control), 60 minutes of ischemia followed by 60 minutes of reperfusion (ISO), or 120 minutes of intraluminal distension (ILD) as part of an inflammatory model. RNA was reverse transcribed into cDNA. NK2 and NK3 primers were designed and mRNA was quantified using real-time PCR for all experimental groups. Results – Expression of NK2 receptor mRNA was highest for the duodenum and the body of the cecum. NK3 mRNA expression had high variability. In the inflammatory model, no statistical significant difference was noted between treatment groups for NK1 or NK3 receptor mRNA. NK2 receptor mRNA expression was significantly decreased for ILD when compared to control. Conclusions –The description of neurokinin receptor mRNA distribution throughout the equine intestinal tract is an important initial step towards determining potential clinical applications of tachykinin agonists and antagonists, as well as their role in gastrointestinal ischemia/reperfusion and intraluminal obstruction injury.

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