scholarly journals ROLE OF SUBSTANCE P IN PANCREATITIS AND ASSOCIATED DISEASES

2021 ◽  
Vol 9 (5) ◽  
pp. 580-590
Author(s):  
Vaishnavi Sundar ◽  
◽  
Shalini Ramasamy ◽  
Sanjana Vimal ◽  
Anupam Dutta ◽  
...  
Keyword(s):  
Substance P ◽  
Neurogenic Inflammation ◽  
Vital Role ◽  
C Fibers ◽  
Inflammatory Processes ◽  
Plasma Leakage ◽  
Neurokinin 1 ◽  
G Protein Coupled ◽  
Crucial Part

Substance P (SP) is a neuropeptide that has its place in the tachykinin family and helps in the transmission of neurogenic signals. SP is also a neuromodulator that plays a crucial part in pain during inflammatory processes. It is produced by the capsaicin-sensitive unmyelinated C fibers sensory neurons by the central and peripheral nervous systems. Substance P is known as a critical primary responder to most of the extreme stimuli, i.e., specifically those with the ability to destabilize the biological integrity. Hence, SP can be considered as an instantaneous system for defense, stress, healing, etc. SP is known to perform a vital role in neurogenic inflammation and the pathophysiology of acute pancreatitis. Out of these, neurogenic inflammation is responsible for acute interstitial pancreatitis as a result of oedema. SP binds itself to the G-protein coupled neurokinin-1 receptor and causes plasma leakage, cell proliferation, and invasion resulting in pancreatic cancer. SP along with comparable neuropeptides seems to be crucial targets with the capability of satisfying several unfulfilled medical requisites. This review article mainly focuses on compiling the available evidence to show that SP could be a novel therapeutic target for pancreatic diseases, and more exploration into the SP signaling pathways is the call of the hour.

scholarly journals Substance P/neurokinin1 receptor is associated with the expression of cardiac stem/pluripotency-associated genes in diabetic right and left atria

2021 ◽  
Author(s):  
Yun-Mi Jeong ◽  
Sora Lee ◽  
Weon Kim
Keyword(s):  
Substance P ◽  
Left Ventricle ◽  
Pcr Analysis ◽  
Diabetic Patients ◽  
Qrt Pcr ◽  
Oletf Rats ◽  
Neurokinin 1 ◽  
The Right ◽  
G Protein Coupled

Abstract Substance P (SP) is a cardioprotective neuropeptide that interacts with the G protein-coupled neurokinin-1 receptor (NK1R). Although the expression of SP/NK1R in the right atrium (RA) of diabetic patients is known to be significantly impaired, the molecular mechanism remains unclear. LETO and OLETF rats were randomly divided into 3 groups: saline, SP injection (5 nmole/kg), and SP+RP injection (1 mg/kg RP67580, a selective non-peptide tachykinin NK1R antagonist). After 3 weeks, the left atrium (LA), RA, and left ventricle (LV) of the rats were collected. Cardiac stem/pluripotency-associated genes in the diabetic atria of each group were comprehensively examined using qRT-PCR analysis. qRT-PCR analysis demonstrated that only the RA of SP-treated OLETF rats exhibited significantly higher levels of alpha-SMA, GATA4, TBX5, and Klf4 in the mRNA, compared to the control. RP prevented the expression of NK1R and four SP-associated genes in the RA of SP-treated OLETF rats. In conclusion, our findings provide novel mechanistic insights into the role of NK1R in diabetic atria.

Paradoxical effect of salbutamol in a model of acute organophosphates intoxication in guinea pigs: role of substance P release

2007 ◽  
Vol 292 (4) ◽  
pp. L915-L923 ◽  
Author(s):  
Jaime Chávez ◽  
Patricia Segura ◽  
Mario H. Vargas ◽  
José Luis Arreola ◽  
Edgar Flores-Soto ◽  
...  
Keyword(s):  
Substance P ◽  
Guinea Pigs ◽  
Smooth Muscle Contraction ◽  
In Vivo Experiments ◽  
Intracellular Ca ◽  
Neurokinin 1 ◽  
Substance P Release

Organophosphates induce bronchoobstruction in guinea pigs, and salbutamol only transiently reverses this effect, suggesting that it triggers additional obstructive mechanisms. To further explore this phenomenon, in vivo (barometric plethysmography) and in vitro (organ baths, including ACh and substance P concentration measurement by HPLC and immunoassay, respectively; intracellular Ca2+ measurement in single myocytes) experiments were performed. In in vivo experiments, parathion caused a progressive bronchoobstruction until a plateau was reached. Administration of salbutamol during this plateau decreased bronchoobstruction up to 22% in the first 5 min, but thereafter airway obstruction rose again as to reach the same intensity as before salbutamol. Aminophylline caused a sustained decrement (71%) of the parathion-induced bronchoobstruction. In in vitro studies, paraoxon produced a sustained contraction of tracheal rings, which was fully blocked by atropine but not by TTX, ω-conotoxin (CTX), or epithelium removal. During the paraoxon-induced contraction, salbutamol caused a temporary relaxation of ∼50%, followed by a partial recontraction. This paradoxical recontraction was avoided by the M2- or neurokinin-1 (NK1)-receptor antagonists (methoctramine or AF-DX 116, and L-732138, respectively), accompanied by a long-lasting relaxation. Forskolin caused full relaxation of the paraoxon response. Substance P and, to a lesser extent, ACh released from tracheal rings during 60-min incubation with paraoxon or physostigmine, respectively, were significantly increased when salbutamol was administered in the second half of this period. In myocytes, paraoxon did not produce any change in the intracellular Ca2+ basal levels. Our results suggested that: 1) organophosphates caused smooth muscle contraction by accumulation of ACh released through a TTX- and CTX-resistant mechanism; 2) during such contraction, salbutamol relaxation is functionally antagonized by the stimulation of M2 receptors; and 3) after this transient salbutamol-induced relaxation, a paradoxical contraction ensues due to the subsequent release of substance P.

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 Metalloelastase in lungs and alveolar macrophages is modulated by extracellular substance P in mice

2008 ◽  
Vol 295 (1) ◽  
pp. L162-L170 ◽  
Author(s):  
J. Xu ◽  
F. Xu ◽  
E. Barrett
Keyword(s):  
Animal Models ◽  
Substance P ◽  
Bronchoalveolar Lavage ◽  
Cigarette Smoke ◽  
Alveolar Macrophages ◽  
Control Medium ◽  
Neurokinin 1 Receptor ◽  
Protein Levels ◽  
C Fibers ◽  
Neurokinin 1

Metalloelastase (MMP-12), mainly produced by macrophages, has been shown to play a key role in the pathogenesis of emphysema in animal models. Chronic cigarette smoke increases pulmonary MMP-12, which is closely correlated with an elevation of pulmonary substance P (SP). Because alveolar macrophages (AMs) contain the neurokinin-1 receptor (NK1R), we tested whether SP was able to trigger the upregulation of MMP-12 synthesis in AMs by acting on the NK1R. AMs isolated from bronchoalveolar lavage cells in C3H/HeN mice were cultured with control medium or SP that was coupled without or with NK1R antagonists (CP-99,994 or aprepitant) for 24 h. We found that SP significantly increased the mRNA of MMP-12 and NK1R by 11-fold and 82%, respectively, in AMs ( P < 0.05), and these responses were abolished by NK1R antagonists with little change in the cells' viability. Because pulmonary SP is primarily released by bronchopulmonary C-fibers (PCFs), we further asked whether destruction of PCFs would reduce SP and MMP-12. Two groups of mice were pretreated with vehicle and neonatal capsaicin (NCAP) to degenerate PCFs, respectively. Our results show that NCAP treatment significantly decreased mRNA and protein levels of SP associated with a reduction NK1R and MMP-12 in the lungs and AMs. These findings suggest that SP has a modulatory effect on pulmonary MMP-12 by acting on NK1R to trigger MMP-12 syntheses in the AMs.

The Role of Substance P in the Marginal Division of the Neostriatum in Learning and Memory is Mediated Through the Neurokinin 1 Receptor in Rats

2011 ◽  
Vol 36 (10) ◽  
pp. 1896-1902 ◽  
Author(s):  
Xue-mei Liu ◽  
Si Yun Shu ◽  
Chang-chun Zeng ◽  
Ye-feng Cai ◽  
Kui-hua Zhang ◽  
...  
Keyword(s):  
Substance P ◽  
Learning And Memory ◽  
Neurokinin 1 Receptor ◽  
Neurokinin 1 ◽  
Marginal Division

Role of substance P (SP) in development of symptoms of neurogenic inflammation in the oral mucosa of the rat

1993 ◽  
Vol 28 (3) ◽  
pp. 191-196 ◽  
Author(s):  
A. Gyorfi ◽  
A. Fazekas ◽  
F. Irmes ◽  
G. Jakab ◽  
T. Suto ◽  
...  
Keyword(s):  
Substance P ◽  
Oral Mucosa ◽  
Neurogenic Inflammation

scholarly journals Elevated Neurokinin 1-Receptor Expression in uterine products of conception is associated with first trimester Miscarriages

2020 ◽  
Author(s):  
Riffat Mehboob ◽  
Syed Amir Gilani ◽  
Amber Hassan ◽  
Adeel Haider Tirmazi ◽  
Fridoon Jawad Ahmad ◽  
...  
Keyword(s):  
Substance P ◽  
First Trimester ◽  
Receptor Expression ◽  
Diagnostic Biomarkers ◽  
Neurokinin 1 Receptor ◽  
Products Of Conception ◽  
Mother’S Age ◽  
Neurokinin 1 ◽  
First Time

AbstractBackgroundMiscarriage is a common complication of early pregnancy, mostly occurring in first trimester. However, the etiological factors, prognostic and diagnostic biomarkers are not well known. Neurokinin-1 Receptor (NK-1R) is a receptor of tachykinin peptide, Substance P (SP) and has a role in various pathological conditions, cancers but it’s association with miscarriages and significance as a clinicopathological parameter is not studied. Accordingly, the present study aimed to clarify the localization and expression for NK-1R in human retained products of conception. Role of NK-1R is not known in miscarriages.Materials and MethodsNK-1R expression was assessed in products of conception by immunohistochemistry. Protein expression was evaluated using the nuclear labelling index (%).ResultsTen human products of conception tissues were studied by immunohistochemistry to demonstrate the localization of NK-1R. The expression of NK-1R protein was high in all the cases of POCs. NK-1R expression showed no notable differences among different cases of miscarriages irrespective of the mother’s age and gestational age at which the event occurred.ConclusionsExpression of NK-1R was similar in all the cases and it was intense. It shows that dysregulation of NK-1R along with its ligand Substance P might be involved in miscarriages. Our results provide fundamental data regarding this anti-NK-1R strategy. Thus, the present study recommends that SP/NK1R system might, therefore, be considered as an emerging and promising diagnostic and therapeutic strategy against miscarriages. Hence, we report for the first time, the expression and localization of NK-1R in products of conception. We suggest NK-1R antagonist in addition to the Immunoglobulins and Human chorionic gonadotropin, to diagnose and treat spontaneous miscarriages.

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