Photoaffinity Labeling of Mutant Neurokinin-1 Receptors Reveals Additional Structural Features of the Substance P/NK-1 Receptor Complex†

Biochemistry ◽  
2001 ◽  
Vol 40 (8) ◽  
pp. 2530-2539 ◽  
Author(s):  
Douglas Macdonald ◽  
Dale F. Mierke ◽  
Hanzhong Li ◽  
Maria Pellegrini ◽  
Bruce Sachais ◽  
...  
Keyword(s):  
Substance P ◽  
Photoaffinity Labeling ◽  
Structural Features ◽  
Receptor Complex ◽  
Neurokinin 1

Mimicry between neurokinin-1 and fibronectin may explain the transport and stability of increased substance P immunoreactivity in patients with bone marrow fibrosis

Blood ◽  
2001 ◽  
Vol 97 (10) ◽  
pp. 3025-3031 ◽  
Author(s):  
Pranela Rameshwar ◽  
Deval D. Joshi ◽  
Prem Yadav ◽  
Jing Qian ◽  
Pedro Gascon ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Substance P ◽  
Mononuclear Cells ◽  
Cdna Probe ◽  
Structural Features ◽  
Cdna Libraries ◽  
Future Research ◽  
Computer Assisted ◽  
Partial Clone ◽  
Neurokinin 1

Abstract Bone marrow (BM) fibrosis may occur in myeloproliferative diseases, lymphoma, myelodysplastic syndrome, myeloma, and infectious diseases. In this study, the role of substance P (SP), a peptide with pleiotropic functions, was examined. Some of its functions—angiogenesis, fibroblast proliferation, and stimulation of BM progenitors—are amenable to inducing BM fibrosis. Indeed, a significant increase was found in SP-immunoreactivity (SP-IR) in the sera of patients with BM fibrosis (n = 44) compared with the sera of patients with hematologic disorders and no histologic evidence of fibrosis (n = 46) (140 ±12 vs 18 ±3; P < .01). Immunoprecipitation of sera SP indicated that this peptide exists in the form of a complex with other molecule(s). It was, therefore, hypothesized that SP might be complexed with NK-1, its natural receptor, or with a molecule homologous to NK-1. To address this, 3 cDNA libraries were screened that were constructed from pooled BM stroma or mononuclear cells with an NK-1 cDNA probe. A partial clone (clone 1) was retrieved that was 97% homologous to the ED-A region of fibronectin (FN). Furthermore, sequence analyses indicated that clone 1 shared significant homology with exon 5 of NK-1. Immunoprecipitation and Western blot analysis indicated co-migration of SP and FN in 27 of 31 patients with BM fibrosis. Computer-assisted molecular modeling suggested that similar secondary structural features between FN and NK-1 and the relative electrostatic charge might explain a complex formed between FN (negative) and SP (positive). This study suggests that SP may be implicated in the pathophysiology of myelofibrosis, though its role would have to be substantiated in future research.

scholarly journals Further Definition of the Substance P (SP)/Neurokinin-1 Receptor Complex

2000 ◽  
Vol 276 (14) ◽  
pp. 10589-10593 ◽  
Author(s):  
Hanzhong Li ◽  
Douglas M. Macdonald ◽  
Xiaoping Hronowski ◽  
Catherine E. Costello ◽  
Susan E. Leeman ◽  
...  
Keyword(s):  
Substance P ◽  
Receptor Complex ◽  
Neurokinin 1 Receptor ◽  
Neurokinin 1 ◽  
Definition Of

scholarly journals Need for Flexible Adjustment of the Treatment Schedule for Aprepitant Administration against Erlotinib-Induced Refractory Pruritus and Skin Rush

2019 ◽  
Vol 12 (1) ◽  
pp. 84-90 ◽  
Author(s):  
Nobuhiko Seki ◽  
Ryosuke Ochiai ◽  
Terunobu Haruyama ◽  
Masashi Ishihara ◽  
Maika Natsume ◽  
...  
Keyword(s):  
Substance P ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Stage Iv ◽  
Subsequent Treatment ◽  
Treatment Schedule ◽  
Weekly Schedule ◽  
Patient Centered ◽  
Neurokinin 1 ◽  
Dermatological Side Effects

Common dermatological side-effects associated with erlotinib, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), include pruritus and skin rash, which are mediated by substance P, leading to the occasional discontinuation of cancer treatment. Aprepitant is an antagonist of neurokinin-1 receptor, through which substance P activates the pruritogens. Thus, aprepitant is expected to offer a promising option for the treatment of erlotinib-induced pruritus. However, the appropriate treatment schedule for aprepitant administration is under consideration. Here, we discuss the need for flexible adjustment of the treatment schedule for aprepitant administration against erlotinib-induced refractory pruritus and skin rush. A 71-year-old female smoker presented with stage IV EGFR-mutated lung adenocarcinoma. She was started on erlotinib at 150 mg/day. However, by 28 days, severe pruritus and acneiform skin rush resistant to standard therapies occurred, resulting in the interruption of erlotinib therapy. After recovery, she was restarted on erlotinib at 100 mg/day. However, severe pruritus and skin rush developed again within 2 weeks. Then, we started the first 3-day dose of aprepitant (125 mg on day 1, 80 mg on day 3, and 80 mg on day 5) based on the results of the previous prospective study, which showed the success rate of 100% with at least the second dose of aprepitant. However, the pruritus and skin rush exacerbated again within 4 weeks. Therefore, we started the second 3-day dose of aprepitant, but in vain. At this point, as the patient-centered medicine, bi-weekly schedule of the 3-day dose of aprepitant was considered and, then, adopted. As the results, the pruritus and skin rush remained well-controlled throughout the subsequent treatment with erlotinib.

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.

scholarly journals Substance P Signaling Contributes to Granuloma Formation inTaenia crassicepsInfection, a Murine Model of Cysticercosis

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Armandina Garza ◽  
David J. Tweardy ◽  
Joel Weinstock ◽  
Balaji Viswanathan ◽  
Prema Robinson
Keyword(s):  
Substance P ◽  
Potential Role ◽  
Cytokine Production ◽  
Taenia Solium ◽  
Granuloma Formation ◽  
Wild Type ◽  
Granulomatous Reaction ◽  
Pain Transmission ◽  
Neurokinin 1 ◽  
The Brain

Cysticercosis is an infection with larval cysts of the cestodeTaenia solium. Through pathways that are incompletely understood, dying parasites initiate a granulomatous reaction that, in the brain, causes seizures. Substance P (SP), a neuropeptide involved in pain-transmission, contributes to inflammation and previously was detected in granulomas associated with deadT. crassicepscysts. To determine if SP contributes to granuloma formation, we measured granuloma-size and levels of IL-1β, TNF-α, and IL-6 within granulomas inT. crassiceps-infected wild type (WT) mice and mice deficient in SP-precursor (SPP) or the SP-receptor (neurokinin 1, NK1). Granuloma volumes of infected SPP- and NK1-knockout mice were reduced by 31 and 36%, respectively, compared to WT mice (P<.05for both) and produced up to 5-fold less IL-1β, TNF-α, and IL-6 protein. Thus, SP signaling contributes to granuloma development and proinflammatory cytokine production inT. crassicepsinfection and suggests a potential role for this mediator in human cystercercosis.

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
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