scholarly journals Ion Channels Involved in Substance P-Mediated Nociception and Antinociception

2019 ◽  
Vol 20 (7) ◽  
pp. 1596 ◽  
Author(s):  
Chu-Ting Chang ◽  
Bo-Yang Jiang ◽  
Chih-Cheng Chen
Keyword(s):  
Amino Acid ◽  
Ion Channels ◽  
Substance P ◽  
Drug Development ◽  
Cell Types ◽  
Analgesic Drug ◽  
Differential Cell ◽  
Neurokinin 1

Substance P (SP), an 11-amino-acid neuropeptide, has long been considered an effector of pain. However, accumulating studies have proposed a paradoxical role of SP in anti-nociception. Here, we review studies of SP-mediated nociception and anti-nociception in terms of peptide features, SP-modulated ion channels, and differential effector systems underlying neurokinin 1 receptors (NK1Rs) in differential cell types to elucidate the effect of SP and further our understanding of SP in anti-nociception. Most importantly, understanding the anti-nociceptive SP-NK1R pathway would provide new insights for analgesic drug development.

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 Calnexin revealed as an ether-a-go-go chaperone by getting mutant worms up and going

2018 ◽  
Vol 150 (8) ◽  
pp. 1059-1061
Author(s):  
Jonathan T. Pierce
Keyword(s):  
Ion Channels ◽  
Dynamic Control ◽  
Cell Types ◽  
K Channel ◽  
Membrane Domains ◽  
Excitable Cells ◽  
Patch Clamp Recording ◽  
Cell Excitability ◽  
Distinct Membrane

The role of ion channels in cell excitability was first revealed in a series of voltage clamp experiments by Hodgkin and Huxley in the 1950s. However, it was not until the 1970s that patch-clamp recording ushered in a revolution that allowed physiologists to witness how ion channels flicker open and closed at angstrom scale and with microsecond resolution. The unexpectedly tight seal made by the patch pipette in the whole-cell configuration later allowed molecular biologists to suck up the insides of identified cells to unveil their unique molecular contents. By refining these techniques, researchers have scrutinized the surface and contents of excitable cells in detail over the past few decades. However, these powerful approaches do not discern which molecules are responsible for the dynamic control of the genesis, abundance, and subcellular localization of ion channels. In this dark territory, teams of unknown and poorly understood molecules guide specific ion channels through translation, folding, and modification, and then they shuttle them toward and away from distinct membrane domains via different subcellular routes. A central challenge in understanding these processes is the likelihood that these diverse regulatory molecules may be specific to ion channel subtypes, cell types, and circumstance. In work described in this issue, Bai et al. (2018. J. Gen. Physiol. https://doi.org/10.1085/jgp.201812025) begin to shed light on the biogenesis of UNC-103, a K+ channel found in Caenorhabditis elegans.

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

scholarly journals Mapping Substance P Binding Sites on the Neurokinin-1 Receptor Using Genetic Incorporation of a Photoreactive Amino Acid

2014 ◽  
Vol 289 (26) ◽  
pp. 18045-18054 ◽  
Author(s):  
Louise Valentin-Hansen ◽  
Minyoung Park ◽  
Thomas Huber ◽  
Amy Grunbeck ◽  
Saranga Naganathan ◽  
...  
Keyword(s):  
Amino Acid ◽  
Substance P ◽  
Binding Sites ◽  
Neurokinin 1 Receptor ◽  
Neurokinin 1 ◽  
Genetic Incorporation

Hypernociceptive role of cytokines and chemokines: Targets for analgesic drug development?

2006 ◽  
Vol 112 (1) ◽  
pp. 116-138 ◽  
Author(s):  
Waldiceu A. Verri ◽  
Thiago M. Cunha ◽  
Carlos A. Parada ◽  
Stephen Poole ◽  
Fernando Q. Cunha ◽  
...  
Keyword(s):  
Drug Development ◽  
Analgesic Drug ◽  
Cytokines And Chemokines

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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