Roles of Substance P in Gastrointestinal Functions and Neuroimmune Interactions

Vilisaar, Janek; Arsenescu, Razvan

doi:10.1007/978-3-319-28609-9_4

Cited by 7 publications

(8 citation statements)

References 117 publications

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“…This study reports for the first time about the detailed expression of NK-1R in products of conception at an early gestational age in first trimester. Secondly, SP/NK-1 receptor system dysregulation may be involved in pathology of pregnancy, such as abortion [15,16], pre-eclampsia [25] and pre-term birth. We describe here for the first time the immunolocalization of NK-1R in human POCs and we provide evidence that NK-1R is expressed in the nucleus.…”

Section: Discussionmentioning

confidence: 99%

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

Mehboob

Gilani

Hassan

et al. 2020

Preprint

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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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Section: Discussionmentioning

confidence: 99%

“…It is also involved in carcinogenesis as reported in many studies and lead to metastasis [11][12][13][14]. SP has a variety of physiological functions in humans, particularly, nervous, immune and cardiovascular systems [15]. Mainly, SP is a braingut hormone, and its receptor is present in brain regions but also in peripheral tissues.…”

Section: Introductionmentioning

confidence: 95%

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

Mehboob

Gilani

Hassan

et al. 2020

Preprint

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“…As well as mediating motor and sensory functions, the vagus nerve could modulate the local immune response through substances such as substance P, a regulator of intestinal motility and secretion in the enteric nervous system. This can bind to receptors on macrophages, dendritic cells and lymphocytes to influence the inflammatory response . The vagus nerve itself is highly sensitive to IL‐1β and LPS, and stimulation has been shown to alter intracerebral cytokine profiles .…”

Section: Additional Host–microbiome Interactionsmentioning

confidence: 99%

“…This can bind to receptors on macrophages, dendritic cells and lymphocytes to influence the inflammatory response. 57 The vagus nerve itself is highly sensitive to IL-1b and LPS, and stimulation has been shown to alter intracerebral cytokine profiles. 56,58 Given the predilection of MS lesions for the brainstem, it is conceivable that demyelination could result in maladaptive immune responses in the intestine, and establish a positive feedback loop through the vagus nerve and circulation (Fig.…”

Section: Additional Host-microbiome Interactionsmentioning

confidence: 99%

Gastrointestinal influences in multiple sclerosis: Focus on the role of the microbiome

Francis

Constantinescu

2018

Clinical & Exp Neuroim

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Despite extensive research, the etiology of multiple sclerosis remains unclear. Gene–environment interactions are believed to determine the risk of disease, but the necessary exposures have not been identified. Here, we review the evidence for the role of disturbances in the normal intestinal flora (the gut microbiome) in the pathogenesis of multiple sclerosis. We present data from human and animal studies proposing that the intestinal immune system integrates bacterial signaling with systemic inflammatory and regulatory responses. Dysbiosis, which is observed more frequently in multiple sclerosis than in health, can skew the intestinal T‐cell repertoire towards an effector T‐cell response, which is subsequently amplified in different tissues. In patients with a genetically determined predisposition, this could lead to inflammation and demyelination in the central nervous system. Furthermore, bacterial products can directly affect the blood–brain barrier, neurons and microglia, and bacterial antigens that mimic neuro‐antigens can lead to activation and proliferation of autoreactive T cells.

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“…According to many studies, SP is one of the key factors of the neuro-immune cross talk during inflammation (Vilisaar and Arsenescu 2016; O’Connor et al 2004). The peptide is also extensively expressed in the enteric neurons during physiological conditions and it is known to regulate smooth muscles activity (Schmidt and Holst 2000).…”

Section: Introductionmentioning

confidence: 99%

Gastric ulcer induced changes in substance P and Nk1, Nk2, Nk3 receptors expression in different stomach localizations with regard to intrinsic neuronal system

Załęcki

2018

Histochem Cell Biol

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Gastric ulceration, a focal tissue damage accompanied by inflammation, can influence other parts of the stomach. Substance P and its receptors are strongly involved in regulation of gastrointestinal motility, secretion and inflammation. The enteric nervous system is one of the regulators of gastrointestinal functioning and contributes to tissue response to the pathology. The pig, an omnivorous animal, is a valuable species for gastrointestinal experiments. Thus, the objective of the study was to verify whether the antral ulceration induces changes in the expression of substance P and tachykinin receptors in the neighboring (antrum) and distanced (corpus, pylorus) porcine gastric tissues and therein localized myenteric and submucosal perikarya as well as in the intrinsic descending neurons supplying pyloric sphincter. The experiment was performed on healthy pigs and pigs with experimentally induced gastric ulcers. Stomach samples from the corpus, antrum (adjacent to the ulcer in experimental pigs) and pylorus were analyzed by: (1) double immunofluorescence for changes in the number of SP-positive myenteric and submucosal neurons (2) Real-Time PCR for changes in expression of mRNA encoding SP and Nk1, Nk2, Nk3 receptors. Additionally, gastric descending neurons supplying pyloric sphincter were immunostained for SP. In experimental animals, only the number of SP-positive myenteric perikarya significantly increased in all stomach localizations studied. Q-PCR revealed increased expression for: SP, Nk1, Nk3 in the corpus; Nk2 and Nk3 in the pylorus; In the antrum, expression of Nk3 was increased but Nk2-decreased. Antral ulcers induced significant changes in the expression of SP and tachykinin receptors in the wide stomach area indicating sophisticated tissue reaction.

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Roles of Substance P in Gastrointestinal Functions and Neuroimmune Interactions

Cited by 7 publications

References 117 publications

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

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

Gastrointestinal influences in multiple sclerosis: Focus on the role of the microbiome

Gastric ulcer induced changes in substance P and Nk1, Nk2, Nk3 receptors expression in different stomach localizations with regard to intrinsic neuronal system

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