Neurokinin-1 Receptor Research Articles

Cost-effectiveness of palonosetron and dexamethasone-based triple and quadruple regimens in preventing highly emetogenic chemotherapy-induced nausea and vomiting

Objective Cost-effectiveness analyses that consider all currently used antiemetics in the case of emetogenic chemotherapy-induced nausea and vomiting (CINV) have not been performed yet. We aim to compare the cost-effectiveness of olanzapine (OLA), or/and neurokinin-1 receptor antagonists (NK-1-RAs), in combination with palonosetron (PAL) and dexamethasone (DEX) in preventing highly emetogenic CINV. Methods Two decision analytic models were constructed. The first model was based on overall complete response (CR); the second model was based on rate of absence of nausea. Four antiemetic regimens PAL + DEX, NK-1-RAs + PAL + DEX, OLA + PAL + DEX, and PAL + NK-1-RA + DEX + OLA were compared in terms of cost, overall CR and rate of absence of nausea. Base case incremental cost-effectiveness ratio (ICER) estimates were calculated. The study was from the US payer perspective. Results In terms of CR, the PAL + NK-1-RA + DEX + OLA was associated with the highest gains in the percentage of CR among all treatment regimens at base case ICERs of $4220 versus PAL + DEX, $4656 versus NK-1-RA + PAL + DEX, $16,471 versus OLA + PAL + DEX. In term of rate of absence of nausea, the PAL + NK-1-RA + DEX + OLA was associated with the highest rate of absence of nausea among all the treatment regimens at base case ICERs of $2291 versus PAL + DEX, $1304 versus NK-1-RA + PAL + DEX, $2657 versus OLA + PAL + DEX. Conclusion from an economic perspective, our study revealed that whether to use overall CR or/and rate of absence of nausea as determinants in the antiemetic decision for the CINV patients, the CR-based-, and rate of absence of nausea-based cost-effectiveness analyses, showed negotiable ICER estimates for the treatment PAL + NK-1-RA + DEX + OLA over the combinations PAL + DEX, NK-1-RA + PAL + DEX, and OLA + PAL + DEX regimens.

Neuropeptidergic regulation of compulsive ethanol seeking in C. elegans

Despite the catastrophic consequences of alcohol abuse, alcohol use disorders (AUD) and comorbidities continue to strain the healthcare system, largely due to the effects of alcohol-seeking behavior. An improved understanding of the molecular basis of alcohol seeking will lead to enriched treatments for these disorders. Compulsive alcohol seeking is characterized by an imbalance between the superior drive to consume alcohol and the disruption or erosion in control of alcohol use. To model the development of compulsive engagement in alcohol seeking, we simultaneously exploited two distinct and conflicting Caenorhabditis elegans behavioral programs, ethanol preference and avoidance of aversive stimulus. We demonstrate that the C. elegans model recapitulated the pivotal features of compulsive alcohol seeking in mammals, specifically repeated attempts, endurance, and finally aversion-resistant alcohol seeking. We found that neuropeptide signaling via SEB-3, a CRF receptor-like GPCR, facilitates the development of ethanol preference and compels animals to seek ethanol compulsively. Furthermore, our functional genomic approach and behavioral elucidation suggest that the SEB-3 regulates another neuropeptidergic signaling, the neurokinin receptor orthologue TKR-1, to facilitate compulsive ethanol-seeking behavior.

Skin codelivery of contact sensitizers and neurokinin-1 receptor antagonists integrated in microneedle arrays suppresses allergic contact dermatitis

Allergic contact dermatitis (CD) is a chronic inflammatory skin disease caused by type 1 biased adaptive immunity for which there is an unmet need for antigen (Ag)-specific immunotherapies. Exposure to skin sensitizers stimulates secretion of the proinflammatory neuropeptides substance P and hemokinin 1, which signal via the neurokinin-1 receptor (NK1R) to promote the innate and adaptive immune responses of CD. Accordingly, mice lacking the NK1R develop impaired CD. Nonetheless, the role and therapeutic opportunities of targeting the NK1R in CD remain to be elucidated. We sought to develop an Ag-specific immunosuppressive approach to treat CD by skin codelivery of hapten and NK1R antagonists integrated in dissolvable microneedle arrays (MNA). Invivo mouse models of contact hypersensitivity and exvivo models of human skin were used to delineate the effects and mechanisms of NK1R signaling and the immunosuppressive effects of the contact sensitizer NK1R antagonist MNA in CD. We demonstrated in mice that CD requires NK1R signaling by substance P and hemokinin 1. Specific deletion of the NK1R in keratinocytes and dendritic cells, but not in mast cells, prevented CD. Skin codelivery of hapten or Ag MNA inhibited neuropeptide-mediated skin inflammation in mouse and human skin, promoted deletion of Ag-specific effector T cells, and increased regulatory T cells, which prevented CD onset and relapses locally and systemically in an Ag-specific manner. Immunoregulation by engineering localized skin neuroimmune networks can be used to treat cutaneous diseases that like CD are caused by type 1 immunity.

Substance P modulates BMSCs migration for tissue repair through NK-1R/CXCR4/p-Akt signal activation.

The migration of bone marrow-derived mesenchymal stem cells (BMSCs) to the wound site played an important role in tissue repair. Substance P (SP) has been studied and reported to be involved in tissue repair by promoting the growth of endothelial cells and the migration of BMSCs. However, the complicated process and the molecular mechanisms were not fully understood. Thus, we aimed to investigate the effect of SP-induced BMSCs migration on tissue repair and its possible mechanism. Western blot and q-PCR assay revealed that SP could induce the BMSCs migration through overexpression of CXCR4 and upregulation of Akt phosphorylation. And the upregulation was related to the activation of neurokinin-1 receptor (NK-1R). Besides, we found that the increased phosphorylation Akt caused by SP could be canceled by the inhibition of CXCR4 both in vitro and in vivo. Furthermore, a skin-injury animal model was established and used to observe the tissue repair process. Results showed that SP could accelerate wound closure, gain more granulation tissue accumulation, and more collagen deposition through the promotion of angiogenesis and induction of the BMSCs migration to the wound site. And these effects could be impaired by inhibition of CXCR4 and p-Akt. Our results suggested that SP promoted tissue repair through BMSCs migration via upregulation of CXCR4 and p-Akt. The expression of CXCR4 and p-Akt were regulated by NK-1R activation. These findings add more evidence in understanding the mechanisms of SP-induced BMSCs migration and highlight the potential for clinical implementation of SP in tissue repair.

Immunolocalization of neurokinin 1 receptor in WHO grade 4 astrocytomas, oral squamous cell and urothelial carcinoma.

Neurokinin-1 receptor (NK-1R) induces inflammatory reactions in peripheral tissues but its regulatory effects in target tissues is dependent on receptor signalling. Substance P (SP) has a high affinity for the NK-1R, to which it binds preferentially. We aimed to investigate the expression of NK-1R in World Health Organization (WHO) grade 4 astrocytomas as well as in oral squamous cell carcinoma (OSCC) and urothelial carcinoma, and its association with disease progression. The study included tissue samples from 19 brain astrocytomas, 40 OSCCs and 10 urothelial carcinomas. NK-1R expression was quantitatively assessed in the tumour cells using immunohistochemistry. The relationship between NK-1R expression in astrocytomas and recurrence-free interval has been explored. The results showed that the NK-1R was intensely expressed in patients with WHO grade 4 astrocytoma, OSCC and urothelial carcinoma. However, cases clinically diagnosed as a low-grade cancer showed reduced NK-1R expression. NK-1R is overexpressed in all cases of WHO grade 4 astrocytoma, OSCC and urothelial carcinoma. The ubi-quitous presence of SP/NK-1R complex during tumour development and progression suggests a possible therapeutic key strategy to use NK-1R antagonist as an adjuvant therapy in the future.

Role of Substance P in Regulating Micro-Milieu of Inflammation in Alopecia Areata.

BackgroundAlopecia areata (AA) is an autoimmune disease characterized by chronic inflammation, the pathogenesis of which is unknown. Stress is believed to play a role; however, evidence remains insufficient. A recent study showed that substance P (SP) damaged hair follicles by causing neurogenic inflammation, activating perifollicular mast cells, and inducing keratinocyte apoptosis.ObjectiveWe aimed at studying the role of SP in AA pathogenesis. We investigated the SP levels in the lesional scalp tissues and serum. We also studied the effect of SP on the inflammatory response and hair growth in the outer root sheath (ORS) cells.MethodsWe compared the serum levels of SP in 58 AA patients and 28 healthy subjects. Then, we checked the expression of SP and SP receptor, neurokinin-1 receptor (NK-1R) in the scalps of AA patients and healthy controls using immunohistochemical staining. Finally, we analyzed the mRNA expression of inflammatory cytokines and hair growth-related factors in ORS cells.ResultsSP and NK-1R expression were markedly higher in the hair follicles and interfollicular epidermis of the scalp lesions of AA patients. However, there was no statistically significant difference in serum SP levels between controls and patients, regardless of the type of alopecia. SP significantly increased the mRNA expression of inflammatory cytokines and decreased hair growth-related growth factors in ORS cells, but the results were not dramatic.ConclusionSP triggered a localized micro-inflammation in lesional hair follicles, provoked an inflammatory response, and inhibited hair growth, thereby confirming the pathogenic role of SP in AA.

Neurokinin-1 receptor promotes non-small cell lung cancer progression through transactivation of EGFR

Despite the great advances in target therapy, lung cancer remains the top cause of cancer-related death worldwide. G protein-coupled receptor neurokinin-1 (NK1R) is shown to play multiple roles in various cancers; however, the pathological roles and clinical implication in lung cancer are unclarified. Here we identified NK1R as a significantly upregulated GPCR in the transcriptome and tissue array of human lung cancer samples, associated with advanced clinical stages and poor prognosis. Notably, NK1R is co-expressed with epidermal growth factor receptor (EGFR) in NSCLC patients’ tissues and co-localized in the tumor cells. NK1R can crosstalk with EGFR by interacting with EGFR, transactivating EGFR phosphorylation and regulating the intracellular signaling of ERK1/2 and Akt. Activation of NK1R promotes the proliferation, colony formation, EMT, MMP2/14 expression, and migration of lung cancer cells. The inhibition of NK1R by selective antagonist aprepitant repressed cell proliferation and migration in vitro. Knockdown of NK1R significantly slowed down the tumor growth in nude mice. The sensitivity of lung cancer cells to gefitinib/osimertinib is highly increased in the presence of the selective NK1R antagonist aprepitant. Our data suggest that NK1R plays an important role in lung cancer development through EGFR signaling and the crosstalk between NK1R and EGFR may provide a potential therapeutic target for lung cancer treatment.

Substance P and Neurokinin 1 Receptor in Chronic Inflammation and Cancer of the Head and Neck: A Review of the Literature.

Head and neck cancer is a growing worldwide public health problem, accounting for approximately 1,500,000 new cases and 500,000 deaths annually. Substance P (SP) is a peptide of the tachykinin family, which has roles related to a large number of physiological mechanisms in humans. The implications of SP in carcinogenesis have recently been reported through the stimulation of the neurokinin 1 receptor (NK1R), or directly, through the effects derived from the constitutive activation of NK1R. Consequently, SP/NK1R seems to play relevant roles in cancer, upregulating cell proliferation, cell migration and chronic inflammation, among other oncogenic actions. Furthermore, there is growing evidence pointing to a central role for SP in tumour progression, singularly so in laryngeal and oral squamous cell carcinomas. The current narrative review of the literature focuses on the relationship between the SP/NK1R system and chronic inflammation and cancer in the head-and-neck region. We described a role for SP/NK1R in the transition from chronic inflammation of the head and neck mucosa, to preneoplastic and neoplastic transformation and progression.

The roles of kisspeptin and neurokinin B in GnRH pulse generation in humans, and their potential clinical application.

The delivery of gonadotropin-releasing hormone (GnRH) in a pulsatile mode to the gonadotropes has long been known to be essential for normal reproductive function. There have been numerous studies aimed at dissecting out the mechanisms underlying GnRH pulse generation. The discovery of kisspeptin as an upstream regulator of GnRH attracted the possibility that pulsatile kisspeptin governed the pulsatile secretion of GnRH. Subsequent studies have shown the importance of the neurokinin B (NKB) system in modulating kisspeptin secretion and this GnRH. A number of studies in laboratory rodents have supported this notion. By contrast, we present data from clinical studies in men and women, in a range of contexts, showing that continuous infusion of kisspeptin 10 at receptor-saturating levels gives rise to an increase in luteinizing hormone (LH) (GnRH) pulse frequency. This has been demonstrated in normal healthy and hypogonadal men, in normal women during the mid-cycle LH surge, in men and women with mutations in the genes encoding NKB or its receptor, neurokinin 3 receptor (NK3R), in women with polycystic ovary syndrome treated with NK3R antagonist, and in women treated with NK3R antagonist during the LH surge. These finds indicate that pulsatile secretion and action of kisspeptin on GnRH neurons is not required for the generation of LH (GnRH) pulses in humans. We also report that there is an absence of desensitization in humans exposed to continuous infusion of kisspeptin-10 at receptor-saturating concentrations over 22h and briefly review GnRH, kisspeptin and NKB analogs and their clinical application.

The Neurokinin-1 Receptor Is a Target in Pediatric Rhabdoid Tumors.

Rhabdoid tumors (RT) are among the most aggressive tumors in early childhood. Overall survival remains poor, and treatment only effectively occurs at the cost of high toxicity and late adverse effects. It has been reported that the neurokinin-1 receptor/ substance P complex plays an important role in cancer and proved to be a promising target. However, its role in RT has not yet been described. This study aims to determine whether the neurokinin-1 receptor is expressed in RT and whether neurokinin-1 receptor (NK1R) antagonists can serve as a novel therapeutic approach in treating RTs. By in silico analysis using the cBio Cancer Genomics Portal we found that RTs highly express neurokinin-1 receptor. We confirmed these results by RT-PCR in both tumor cell lines and in human tissue samples of various affected organs. We demonstrated a growth inhibitory and apoptotic effect of aprepitant in viability assays and flow cytometry. Furthermore, this effect proved to remain when used in combination with the cytostatic cisplatin. Western blot analysis showed an upregulation of apoptotic signaling pathways in rhabdoid tumors when treated with aprepitant. Overall, our findings suggest that NK1R may be a promising target for the treatment of RT in combination with other anti-cancer therapies and can be targeted with the NK1R antagonist aprepitant.

Tachykinins amplify the action of capsaicin on central histaminergic neurons

Substance P (SP), a product of the tachykinin 1 (Tac1) gene, is expressed in many hypothalamic neurons. Its wake-promoting potential could be mediated through histaminergic (HA) neurons of the tuberomamillary nucleus (TMN), where functional expression of neurokinin receptors (NKRs) waits to be characterized. As in the process of nociception in the peripheral nervous system (PNS) capsaicin-receptor (transient potential vanilloid 1: TRPV1) signalling is amplified by local release of histamine and SP, we tested the involvement of tachykinins in the capsaicin-induced long-lasting enhancement (LLEcaps) of HA neurons firing by investigating selective neurokinin receptor ligands in the hypothalamic mouse brain slice preparation using patch-clamp recordings in cell-attached mode combined with single-cell RT-PCR. We report that the majority of HA neurons respond to SP (EC50 3 nM), express the SP precursor tachykinin 1 (Tac1) gene and at least one of the neurokinin receptors. Responses to selective agonists of three known neurokinin receptors were sensitive to corresponding antagonists. LLEcaps was significantly impaired by the neurokinin receptor antagonists, indicating that in hypothalamus, as in the PNS, release of tachykinins downstream to TRPV1 activation is able to boost the release of histamine. The excitatory action of SP on histaminergic neurons adds another pathway to the noradrenergic and orexinergic ones to synergistically enhance cortical arousal. We show NK1R to play a prominent role on HA neurons and thus the control of wakefulness.

Aprepitant Promotes Caspase-Dependent Apoptotic Cell Death and G2/M Arrest through PI3K/Akt/NF-κB Axis in Cancer Stem-Like Esophageal Squamous Cell Carcinoma Spheres.

The antagonists of the neurokinin-1 receptor (NK1R) are known for their anti-inflammatory, anxiolytic, antiemetic, and anticancer activities. Aprepitant, a nonpeptide NK1R antagonist, is used in nausea and vomiting, the most common side effects of cancer chemotherapy in patients. It has been established that NK1R activation by substance P (SP), which links cancer promotion and progression to a neurokinin-mediated environment, became one mechanism that corresponds to the mitogenesis of tumor cells. Therefore, this study is aimed at explaining and evaluating the anticancer impacts of aprepitant on esophageal squamous cancer cell (ESCC) spheres by using in vitro experiments, such as resazurin, ROS, annexin-V binding, RT-PCR, and Western blot analysis. As a result, we showed that aprepitant had strong antiproliferative and cytotoxic effects on ESCC cell spheres. Also, aprepitant caused significant G2-M cell cycle arrest depending on concentration increase. Further, exposure of cells to this agent resulted in caspase -8/-9-dependent apoptotic pathway activation by modifying the expression of genes involved in apoptosis. Besides, treatment of the cells by aprepitant abrogates of the PI3K/Akt pathway, as shown by reducing the level of Akt, induces apoptotic cell death. In summary, pharmacological inhibition of NK1R with aprepitant seems to have a significant chance of treating ESCC as a single agent or in conjunction with other chemotherapeutic drugs.

The SP/NK1R System-Mediated ROS Generation in GBM Cells through Inhibiting Glutaredoxin Protein.

Altered redox balance is among the main contributing factors developing glioblastoma multiforme (GBM), a highly aggressive grade IV brain tumor. Neuropeptide substance P (SP) plays a key role in modifying the cellular redox environment by activating the neurokinin-1 receptor (NK1R). In this study, we aimed to investigate the redox-modulating properties of both SP and a commercially available NK1R antagonist, aprepitant in GBM cells. To detect the effect of aprepitant on the viability of U87 glioblastoma cells, resazurin assay was applied. The level of intracellular ROS was assessed using 2′,7′-dichlorodihydrofluorescein diacetate (H2DCFDA) assay. The expression of glutaredoxin, a well-known redox-active protein, was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Concurrently, the activity of glutaredoxin was also analyzed by a commercial kit (ZellBio GmbH). We found that SP increased the intracellular levels of reactive oxygen species (ROS) in U87 GBM cells, and aprepitant remarkably decreased this effect. We also explored the effects of SP/NK1R signaling on the glutaredoxin system as a major cellular redox buffer in GBM cells. SP reduced both expression and enzymatic activity of glutaredoxin, and these effects were significantly decreased by aprepitant. In conclusion, our results suggest a possible involvement of SP/NK1R signaling in GBM pathogenesis through oxidative stress and offering new insight for the application of aprepitant as a redox-modulating strategy in GBM patients.

Neurokinin receptor mechanisms in forebrain medial septum modulate nociception in the formalin model of inflammatory pain

The present study has explored the hypothesis that neurokinin1 receptors (NK1Rs) in medial septum (MS) modulate nociception evoked on hind paw injection of formalin. Indeed, the NK1Rs in MS are localized on cholinergic neurons which have been implicated in nociception. In anaesthetized rat, microinjection of L-733,060, an antagonist at NK1Rs, into MS antagonized the suppression of CA1 population spike (PS) evoked on peripheral injection of formalin or on intraseptal microinjection of substance P (SP), an agonist at NK1Rs. The CA1 PS reflects the synaptic excitability of pyramidal cells in the region. Furthermore, microinjection of L-733,060 into MS, but not LS, attenuated formalin-induced theta activation in both anaesthetized and awake rat, where theta reflects an oscillatory information processing by hippocampal neurons. The effects of L-733,060 on microinjection into MS were nociceptive selective as the antagonist did not block septo-hippocampal response to direct MS stimulation by the cholinergic receptor agonist, carbachol, in anaesthetized animal or on exploration in awake animal. Interestingly, microinjection of L-733,060 into both MS and LS attenuated formalin-induced nociceptive flinches. Collectively, the foregoing novel findings highlight that transmission at NK1R provide an affective valence to septo-hippocampal information processing and that peptidergic transmission in the septum modulates nociceptive behaviours.

Novel Pituitary Actions of TAC4 Gene Products in Teleost

Tachykinin 4 (TAC4) is the latest member of the tachykinin family involved in several physiological functions in mammals. However, little information is available about TAC4 in teleost. In the present study, we firstly isolated TAC4 and six neurokinin receptors (NKRs) from grass carp brain and pituitary. Sequence analysis showed that grass carp TAC4 could encode two mature peptides (namely hemokinin 1 (HK1) and hemokinin 2 (HK2)), in which HK2 retained the typical FXGLM motif in C-terminal of tachyinin, while HK1 contained a mutant VFGLM motif. The ligand-receptor selectivity showed that HK2 could activate all 6 NKRs but with the highest activity for the neurokinin receptor 2 (NK2R). Interestingly, HK1 displayed a very weak activation for each NKR isoform. In grass carp pituitary cells, HK2 could induce prolactin (PRL), somatolactin α (SLα), urotensin 1 (UTS1), neuromedin-B 1 (NMB1), cocaine- and amphetamine-regulated transcript 2 (CART2) mRNA expression mediated by NK2R and neurokinin receptor 3 (NK3R) via activation cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA), phospholipase C (PLC)/inositol 1,4,5-triphosphate (IP3)/protein kinase C (PKC) and calcium2+ (Ca2+)/calmodulin (CaM)/calmodulin kinase-II (CaMK II) cascades. However, the corresponding stimulatory effects triggered by HK1 were found to be notably weaker. Furthermore, based on the structural base for HK1, our data suggested that a phenylalanine (F) to valine (V) substitution in the signature motif of HK1 might have contributed to its weak agonistic actions on NKRs and pituitary genes regulation.

Cinacalcet Targets the Neurokinin-1 Receptor and Inhibits PKCδ/ERK/P65 Signaling to Alleviate Dextran Sulfate Sodium-Induced Colitis.

Objective: Inflammatory bowel disease is an immune-mediated chronic inflammatory disease of the gastrointestinal tract for which curative drugs are currently not available. This study was performed to assess the therapeutic effects of cinacalcet on dextran sulfate sodium (DSS)-induced colitis. Methods: Primary macrophages obtained from bone marrow and the macrophage cell line RAW264.7 were used to examine the inhibitory effect of cinacalcet on cytokine production, the PKCδ/ERK/P65 signaling pathway, and NF-κB P65 translocation. Colitis was induced using DSS to assess the treatment effect of cinacalcet. Bioinformatics approaches were adopted to predict potential targets of cinacalcet, and a drug affinity responsive target stability (DARTs) assay was performed to confirm binding between cinacalcet and potential target. Results: In vivo analysis showed that cinacalcet reduced the disease activity score, prevented shortening of the colon, diminished inflammatory cell infiltration, and protected the structural integrity of the intestinal wall. Cinacalcet also reduced production of the inflammatory cytokines TNFα, IL-1β, and IL-6 in the colon and sera of mice with DSS-induced colitis. In vitro studies revealed that cinacalcet suppressed the translocation of P65 and inhibited production of the inflammatory cytokines IL-1β and IL-6. Mechanistic studies revealed that the target of cinacalcet was neurokinin-1 receptor (NK1R) and their binding was confirmed by a DARTs assay. Furthermore, the inhibition of NK-κB P65 activation was found to occur via the suppression of PKCδ/ERK/P65 signaling mediated by cinacalcet. Conclusion: Cinacalcet inhibits the activation of NF-κB and reduces the production of inflammatory cytokines by suppressing the PKCδ/ERK/P65 signaling pathway via targeting NK1R, suggesting that it can be used to treat inflammatory diseases, particularly colitis.

Substance P/ Neurokinin-1 Receptor, Trigeminal Ganglion, Latency, and Coronavirus Infection-Is There Any Link?

Novel Severe Acute Respiratory Syndrome-Corona Virus-2 infection (SARS-CoV-2) is an acute respiratory and infectious disease. This perspective aims to provide a basic understanding of the inflammation caused by SARS-CoV-2 and its relation to the trigeminal ganglion (TG). The virus enters through the mucous membranes of the orofacial region and reaches the TG, where it resides and takes control of its peptides including Substance P (SP). SP is the main neuropeptide, neuromodulator, and neuro-hormone of TG, associated with nociception and inflammation under noxious stimulus. SP release is triggered and, consequently, affects the immune cells and blood vessels to release the mediators for inflammation. Hence, cytokine storm is initiated and causes respiratory distress, bronchoconstriction, and death in complicated cases. Neurokinin-1 Receptor (NK-1R) is the receptor for SP and its antagonists, along with glucocorticoids, may be used to alleviate the symptoms and treat this infection by blocking this nociceptive pathway. SP seems to be the main culprit involved in the triggering of inflammatory pathways in SARS-CoV-2 infection. It may have a direct association with cardio-respiratory rhythm, sleep-wake cycle, nociception, and ventilatory responses and regulates many important physiological and pathological functions. Its over-secretion should be blocked by NK-1R antagonist. However, experimental work leading to clinical trials are mandatory for further confirmation. Here, it is further proposed that there is a possibility of latency in SARS-CoV-2 virus infection if it is acting through TG, which is the main site for other viruses that become latent.

Antiemetics for adults for prevention of nausea and vomiting caused by moderately or highly emetogenic chemotherapy: a network meta-analysis.

Antiemetics for adults for prevention of nausea and vomiting caused by moderately or highly emetogenic chemotherapy: a network meta-analysis.

Potential in vitro therapeutic effects of targeting SP/NK1R system in cervical cancer.

Cervical cancer, an aggressive gynecological cancer, seriously threatens women's health worldwide. It is recently reported that neuropeptide substance P (SP) regulates many tumor-associated processes through neurokinin-1 receptor (NK1R). Therefore, we used cervical cancer cell line (HeLa) to investigate the functional relevance of the SP/NK1R system in cervical cancer pathogenesis. Cellular proliferation and cytotoxicity were analyzed by colorimetric MTT assay. Quantitative real-time PCR (qRT-PCR) was used to measure mRNA expression levels of desired genes. Cell cycle distribution and apoptosis were evaluated by flow cytometry. A wound-healing assay was employed to assess migration ability. We found that the truncated isoform of NK1R(NK1R-Tr) is the dominantly expressed form of the receptor in Hela cells. We also indicated that that SP increased HeLa cell proliferation while treatment with NK1R antagonist, aprepitant, inhibited HeLa cell viability in a dose and time-dependent manner. SP also alters the levels of cell cycle regulators (up-regulation of cyclin B1 along with downregulation of p21) and apoptosis-related genes (up-regulation of Bcl-2 along with downregulation of Bax) while aprepitant reversed these effects. Aprepitant also induced arrest within the G2 phase of the cell cycle and subsequent apoptosis. Furthermore, SP promoted the migrative phenotype of HeLa cells and increased MMP-2 and MMP-9 expression while aprepitant exposure significantly reversed these effects. Collectively, our results indicate the importance of the SP / NK1R system in promoting both proliferative and migrative phenotypes of cervical cancer cells and suggest that aprepitant may be developed as a novel treatment for combating cervical cancer.

NK1 receptor antagonists versus other antiemetics in the prevention of postoperative nausea and vomiting following laparoscopic surgical procedures: a systematic review and meta-analysis.

A systematic electronic search of MEDLINE, EMBASE, and CINAHL databases aimed at comparing neurokinin-1 receptor antagonists with other antiemetics in their prevention of postoperative nausea and vomiting in adult patients undergoing laparoscopic surgery identified seven randomized controlled trials for review and meta-analysis. Preoperative aprepitant 80 mg was found to reduce nausea (RR: 0.56, 95% CI: 0.41–0.75, I2 = 0%, P = 0.89) and vomiting (RR: 0.20, 95% CI: 0.05–0.77, I2 = 0%, P = 0.96) and resulted in complete response (RR: 1.61 (1.25-2.08), I2 = 0%, P = 0.70) within the first 2 hours following surgery as well as vomiting in 2–24 hours (RR: 0.09, 95% CI: 0.02-0.36, I2 = 0%; P = 0.81) when compared to placebo or no antiemetic therapy. Preoperative aprepitant 80 mg has a superior overall effect compared to placebo or other antiemetics in the first two hours postoperatively, and thereafter reduces the risk of vomiting alone in the first 24 hours following laparoscopic surgeries.