scholarly journals Cystathionine-Gamma-Lyase-Derived Hydrogen Sulfide-Regulated Substance P Modulates Liver Sieve Fenestrations in Caecal Ligation and Puncture-Induced Sepsis

2019 ◽  
Vol 20 (13) ◽  
pp. 3191 ◽  
Author(s):  
Ravinder Gaddam ◽  
Stephen Chambers ◽  
Robin Fraser ◽  
Victoria Cogger ◽  
David Le Couteur ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Hydrogen Sulfide ◽  
Substance P ◽  
Liver Sinusoidal Endothelial Cells ◽  
Neurokinin 1 Receptor ◽  
Genetic Deletion ◽  
Encoding Gene ◽  
Neurokinin 1 ◽  
Caecal Ligation And Puncture ◽  
Caecal Ligation

Cystathionine-γ-lyase (CSE) is a hydrogen sulfide (H2S)-synthesizing enzyme that promotes inflammation by upregulating H2S in sepsis. Liver sinusoidal endothelial cells (LSECs) are fenestrated endothelial cells (liver sieve) that undergo alteration during sepsis and H2S plays a role in this process. Substance P (SP) is encoded by the preprotachykinin A (PPTA) gene, and promotes inflammation in sepsis; however, its regulation by H2S is poorly understood. Furthermore, the interaction between H2S and SP in modulating LSEC fenestrations following sepsis remains unclear. This study aimed to investigate whether CSE/H2S regulates SP and the neurokinin-1 receptor (NK-1R) and modulates fenestrations in LSECs following caecal ligation and puncture (CLP)-induced sepsis. Here we report that the absence of either CSE or H2S protects against liver sieve defenestration and gaps formation in LSECs in sepsis by decreased SP-NK-1R signaling. Following sepsis, there is an increased expression of liver CSE and H2S synthesis, and plasma H2S levels, which were aligned with higher SP levels in the liver, lungs and plasma and NK-1R in the liver and lungs. The genetic deletion of CSE led to decreased sepsis-induced SP and NK-1R in the liver, lungs and plasma SP suggesting H2S synthesized through CSE regulates the SP-NK-1R pathway in sepsis. Further, mice deficient in the SP-encoding gene (PPTA) preserved sepsis-induced LSEC defenestration and gaps formation, as seen by maintenance of patent fenestrations and fewer gaps. In conclusion, CSE/H2S regulates SP-NK-1R and modulates LSEC fenestrations in sepsis.

scholarly journals Substance P mediates inflammatory oedema in acute pancreatitis via activation of the neurokinin-1 receptor in rats and mice

2000 ◽  
Vol 130 (3) ◽  
pp. 505-512 ◽  
Author(s):  
Eileen F Grady ◽  
Shandra K Yoshimi ◽  
John Maa ◽  
Dahlia Valeroso ◽  
Robert K Vartanian ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Substance P ◽  
Neurokinin 1 Receptor ◽  
Neurokinin 1 ◽  
Rats And Mice

scholarly journals Substance P enhances HIV-1 infection in human fetal brain cell cultures expressing full-length neurokinin-1 receptor

2013 ◽  
Vol 19 (3) ◽  
pp. 219-227 ◽  
Author(s):  
Lynnae Schwartz ◽  
Sergei V. Spitsin ◽  
John Meshki ◽  
Florin Tuluc ◽  
Steven D. Douglas ◽  
...  
Keyword(s):  
Substance P ◽  
Cell Cultures ◽  
Fetal Brain ◽  
Brain Cell ◽  
Full Length ◽  
Human Fetal Brain ◽  
Neurokinin 1 Receptor ◽  
Brain Cell Cultures ◽  
Neurokinin 1 ◽  
Hiv 1

Action of substance P (neurokinin-1) receptor activation on rat neostriatal projection neurons

Synapse ◽  
1999 ◽  
Vol 33 (1) ◽  
pp. 26-35 ◽  
Author(s):  
Elvira Galarraga ◽  
Salvador Hern�ndez-L�pez ◽  
Dagoberto Tapia ◽  
Arturo Reyes ◽  
Jos� Bargas
Keyword(s):  
Substance P ◽  
Receptor Activation ◽  
Projection Neurons ◽  
Neurokinin 1 Receptor ◽  
Neurokinin 1

scholarly journals Analgesia by deletion of spinal neurokinin 1 receptor expressing neurons using a bioengineered substance P-Pseudomonas exotoxin conjugate

2017 ◽  
Vol 13 ◽  
pp. 174480691772765 ◽  
Author(s):  
Michael J Iadarola ◽  
Matthew R Sapio ◽  
Xunde Wang ◽  
Hector Carrero ◽  
Maria Luisa Virata-Theimer ◽  
...  
Keyword(s):  
Substance P ◽  
Pseudomonas Exotoxin ◽  
Neurokinin 1 Receptor ◽  
Neurokinin 1

Expression of Substance P and Its Neurokinin-1 Receptor on Thymocytes: Functional Relevance in the Regulation of Thymocyte Apoptosis and Proliferation

2002 ◽  
Vol 10 (4) ◽  
pp. 232-246 ◽  
Author(s):  
Giorgio Santoni ◽  
Consuelo Amantini ◽  
Roberta Lucciarini ◽  
Pierluigi Pompei ◽  
Marina Perfumi ◽  
...  
Keyword(s):  
Substance P ◽  
Neurokinin 1 Receptor ◽  
Thymocyte Apoptosis ◽  
Functional Relevance ◽  
Neurokinin 1

scholarly journals Prognostic Significance of Substance P/Neurokinin 1 Receptor and Its Association with Hormonal Receptors in Breast Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Riffat Mehboob ◽  
Syed Amir Gilani ◽  
Amber Hassan ◽  
Sadaf ◽  
Imrana Tanvir ◽  
...  
Keyword(s):  
Breast Carcinoma ◽  
Substance P ◽  
Tumor Cells ◽  
Prognostic Significance ◽  
Positive Staining ◽  
Ki 67 ◽  
Neurokinin 1 Receptor ◽  
Group A ◽  
Neurokinin 1 ◽  
Group B

Expression and immunolocalization of Substance P (SP)/Neurokinin-1 Receptor (NK-1R) in breast carcinoma (BC) patients and its association with routine proliferative markers (ER, PR, HER2/neu, and Ki-67) were evaluated. A cross-sectional study was performed on 34 cases of BC. There were 23 cases of group A (grade III), 8 of group B (grade II), and only 3 cases of group C (grade I). All samples were then processed for SP and NK-1R immunohistochemistry for few cases. 14/23 cases (61%) of group A, 7/8 cases (88%) of group B, and 2/3 (67%) cases of group C were SP positive. Overall, strong staining (≥10% tumor cells), labeled as “+3,” was observed in 9/14 (64.2%) cases of group A and 1/8 (12.5%) cases of group B. Moderate staining labelled as “+2” (in ≥10% tumor cells) was observed in 3/14 (21.4%) cases of group A and 4/8 (50%) cases of group B. Weak positive staining “+1” was observed in only 2/14 (14.28%) cases of group A, 2/8 (25%) cases of group B, and all 2/2 (100%) cases of group C. SP and NK-1R are overexpressed in breast carcinomas, and there is significant association between the grade of tumor and their overexpression.

scholarly journals Effects of General Anesthetics on Substance P Release and c-Fos Expression in the Spinal Dorsal Horn

2013 ◽  
Vol 119 (2) ◽  
pp. 433-442 ◽  
Author(s):  
Toshifumi Takasusuki ◽  
Shigeki Yamaguchi ◽  
Shinsuke Hamaguchi ◽  
Tony L. Yaksh
Keyword(s):  
Nitrous Oxide ◽  
Substance P ◽  
Dorsal Horn ◽  
Receptor Internalization ◽  
General Anesthetics ◽  
Neurokinin 1 Receptor ◽  
P Release ◽  
Fos Expression ◽  
Neurokinin 1 ◽  
Substance P Release

Abstract Background: The authors examined in vivo the effects of general anesthetics on evoked substance P release (primary afferent excitability) and c-Fos expression (neuronal activation) in superficial dorsal horn. Methods: Rats received saline, propofol (100 mg/kg), pentobarbital (50 mg/kg), isoflurane (2 minimum alveolar concentration), nitrous oxide (66%), or fentanyl (30 μg/kg). During anesthesia, rats received intraplantar 5% formalin (50 μl) to left hind paw. Ten minutes later, rats underwent transcardial perfusion with 4% paraformaldehyde. Substance P release from small primary afferents was assessed by incidence of neurokinin 1 receptor internalization in the superficial dorsal horn. In separate studies, rats were sacrificed after 2 h and c-Fos expression measured. Results: Intraplantar formalin-induced robust neurokinin 1 receptor internalization in ipsilateral dorsal horn (ipsilateral: 54 ± 6% [mean ± SEM], contralateral: 12 ± 2%; P < 0.05; n = 4). Fentanyl, but not propofol, pentobarbital, isoflurane, nor nitrous oxide alone inhibited neurokinin 1 receptor internalization. However, 2 minimum alveolar concentration isoflurane + nitrous oxide reduced neurokinin 1 receptor internalization (27 ± 3%; P < 0.05; n = 5). All agents reduced c-Fos expression (control: 34 ± 4, fentanyl: 8 ± 2, isoflurane: 12 ± 3, nitrous oxide: 11 ± 2, isoflurane + nitrous oxide: 12 ± 1, pentobarbital: 11 ± 2, propofol: 13 ± 3; P < 0.05; n = 3). Conclusion: General anesthetics at anesthetic concentrations block spinal neuron activation through a mechanism that is independent of an effect on small primary afferent peptide release. The effect of fentanyl alone and the synergistic effect of isoflurane and nitrous oxide on substance P release suggest a correlative rationale for the therapeutic use of these anesthetic protocols by blocking nociceptive afferent transmitter release and preventing the initiation of cascade, which is immediately postsynaptic to the primary afferent.

scholarly journals The substance P and neurokinin-1 receptor system in human thyroid cancer: an immunohistochemical study

2020 ◽  
Vol 64 (2) ◽  
Author(s):  
Inmaculada Isorna ◽  
Francisco Esteban ◽  
Juan Solanellas ◽  
Rafael Coveñas ◽  
Miguel Muñoz
Keyword(s):  
Thyroid Cancer ◽  
Substance P ◽  
Scoring System ◽  
Therapeutic Strategy ◽  
Human Thyroid ◽  
Follicular Cells ◽  
Receptor System ◽  
Normal Thyroid ◽  
Neurokinin 1 Receptor ◽  
Neurokinin 1

To develop a new therapeutic strategy against thyroid cancer (TC), the expression of both substance P (SP) and neurokinin-1 receptor (NK-1R) must be demonstrated in TC cells. This study aims to examine by immunohistochemistry, the localization of SP and the NK-1R in human TC samples (papillary, follicular, medullary, anaplastic), in metastasis and in healthy thyroid samples. SP and the NK-1R were expressed in all normal and TC samples. In healthy glands, SP was located in follicular cells (nucleus) and colloid and NK-1R in follicular cells (cytoplasm) and stroma. In TC samples, SP was visualized in follicular cells (nucleus and cytoplasm), stroma and colloid and NK-1R in follicular cells (cytoplasm), stroma and colloid. A semiquantitative scoring system (Allred Unit Scoring System) was applied. The expression (Allred total score) of SP and NK-1R was weaker in normal thyroid glands than in TC. In comparison with TC samples, a lower intensity/proportion of SP (nucleus and cytoplasm of follicular cells; stroma) was observed in normal samples. By contrast, in the colloid of TC samples the presence of SP was lower than in normal samples. In comparison with TC samples, the presence of the NK-1R in the cytoplasm of follicular cells and colloid was lower in normal thyroid samples, whereas the expression of this receptor in the stroma was higher. The results reported in this study suggest that the NK-1R could be a new target for the treatment of TC and use of the NK-1R antagonists could serve as a new anti-TC therapeutic strategy.

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