The receptor for substance P is one of the G protein-coupled receptor.
NCBI Summary:
This gene belongs to a gene family of tachykinin receptors. These tachykinin receptors are characterized by interactions with G proteins and contain seven hydrophobic transmembrane regions. This gene encodes the receptor for the tachykinin substance P, also referred to as neurokinin 1. The encoded protein is also involved in the mediation of phosphatidylinositol metabolism of substance P. [provided by RefSeq, Sep 2008]
General function
Receptor
Comment
Cellular localization
Plasma membrane
Comment
Neurokinin 3 receptor antagonism ameliorates key metabolic features in a hyperandrogenic PCOS mouse model. Sucquart IE et al. (2021) Polycystic ovary syndrome (PCOS) is a prevalent endocrine condition characterised by a range of endocrine, reproductive and metabolic abnormalities. At present, management of women with PCOS is suboptimal as treatment is only symptomatic. Clinical and experimental advances in our understanding of PCOS etiology support a pivotal role for androgen neuroendocrine actions in PCOS pathogenesis. Hyperandrogenism is a key PCOS trait and androgen actions play a role in regulating the kisspeptin-/neurokinin B-/dynorphin (KNDy) system. This study aimed to investigate if targeted antagonism of neurokinin B signalling through the neurokinin 3 receptor (NK3R) would reverse PCOS traits in a dihydrotestosterone (DHT)-induced mouse model of PCOS. After 3 months, DHT exposure induced key reproductive PCOS traits of cycle irregularity and ovulatory dysfunction, and PCOS-like metabolic traits including increased body weight; white and brown fat pad weights; fasting serum triglyceride and glucose levels and blood glucose iAUC. Treatment with a NK3R antagonist (MLE4901) did not impact the observed reproductive defects. In contrast, following NK3R antagonist treatment, PCOS-like females displayed decreased total body weight, adiposity and adipocyte hypertrophy, but increased respiratory exchange ratio, suggesting NK3R antagonism altered the metabolic status of the PCOS-like females. NK3R antagonism did not improve circulating serum triglyceride or fasted glucose levels. Collectively, these findings demonstrate that NK3R antagonism may be beneficial in the treatment of adverse metabolic features associated with PCOS and support neuroendocrine targeting in the development of novel therapeutic strategies for PCOS.//////////////////
Miyamoto A, et al 1993 reported multiple effects of neuropeptide Y, substance P and vasoactive
intestinal polypeptide on progesterone and oxytocin release from
bovine corpus luteum in vitro.
The direct effects of neuropeptide Y (NPY),
substance P (SP) and vasoactive intestinal polypeptide (VIP) on the release of
progesterone and oxytocin from midluteal phase CL (days 8-12) were examined in
vitro. Long-term as well as short-term effects were assessed using both a
serum-reduced luteal cell culture and a microdialysis system (MDS) of luteal
tissue. In the long-term experiments, luteal cells were preincubated from the start
of the culture for 48 h with NPY, SP and VIP (10 pmol/1-100 nmol/l). During the
following 4 h the neuropeptides showed a dose-dependent stimulation of
progesterone release, but there was no effect on oxytocin release. LH showed a
synergistic effect with NPY, SP and VIP on progesterone release. In the short-term
experiments, the neuropeptides were added 48 h after the start of the culture. All
three peptides were most stimulatory to LH-supported progesterone release 30
min after addition, and the effect decreased greatly thereafter to the control level
from 60 to 120 min.
Pitzel L, et al 1991 reported the effects of substance-P and neuropeptide-Y on in vitro steroid release by porcine
granulosa and luteal cells.
Expression regulated by
Comment
Ovarian localization
Luteal cells
Comment
Expression of NK1 receptor at the protein and mRNA level in the porcine female reproductive system. Bukowski R et al. (2014) The presence and distribution of substance P (SP) receptor NK1 was studied in the ovary, the oviduct and the uterus (uterine horn and cervix) of the domestic pig using the methods of molecular biology (RT-PCR and immunoblot) and immunohistochemistry. The expression of NK1 receptor at mRNA level was confirmed with RT-PCR in all the studied parts of the porcine female reproductive system by the presence of 525 bp PCR product and at the protein level by the detection of 46 kDa protein band in immunoblot. Immunohistochemical staining revealed the cellular distribution of NK1 receptor protein. In the ovary NKI receptor was present in the wall of arterial blood vessels, as well as in ovarian follicles of different stages of development. In the tubular organs the NK1 receptor immunohistochemical stainings were observed in the wall of the arterial blood vessels, in the muscular membrane, as well as in the mucosal epithelium. The study confirmed the presence of NK1 receptor in the tissues of the porcine female reproductive tract which clearly points to the possibility that SP can influence porcine ovary, oviduct and uterus.//////////////////
Reibiger I, et al 2001 reported the expression of substance P and its neurokinin-1 receptor
mRNA in the bovine corpus luteum of early developmental stage.
Substance P was depicted by using
indirect immunohistology and immunofluorescence localization. The dot blot
analysis confirmed the presence of SP at the protein level.
The mRNA for SP and for the NK-1 receptor were detected in the corpus
luteum of early developmental stage with RT-PCR and nested RT-PCR. The production of SP and the expression of NK-1 receptor mRNA may be
involved in the selective recruitment of eosinophils into the bovine corpus
Follicle stages
Antral, Preovulatory, Corpus luteum
Comment
Coexpression of preprotachykinin A and B transcripts in the bovine corpus luteum and evidence for functional neurokinin receptor activity in luteal endothelial cells and ovarian macrophages Brylla E, et al .
Nonneuronal cell sources of tachykinins, such as substance P (SP) and neurokinin B (NKB), have been demonstrated in leukocytes, endothelial cells and endocrine cells, and may play a role in corpus luteum (CL) development. For this reason, we analyzed mRNA presence for the two tachykinin precursors together with the neurokinin-1 receptor and the neurokinin-3 receptor (NK-1R and NK-3R, preferred by SP and NKB, respectively) in bovine CL at various stages in the luteal phase. Using the RT-PCR technique, we detected coexpression for the preprotachykinin A gene (PPT-A), which encodes SP and neurokinin A (NKA), and the preprotachykinin B gene (PPT-B) for NKB in the CL at the development, secretion and regression stages. Coexpression was also noted for NK-1R and NK-3R gene transcripts. Cultures of endothelial cells (ECs) derived from bovine CL expressed NK-1R and NK-3R mRNA, as did ovarian macrophages. Agonist treatment induced a stronger intracellular calcium ([Ca(2+)](i)) increase after activation of NK-1R compared to NK-3R, a result that we verified by calcium imaging. This is the first evidence for functional tachykinin receptor activity in luteal ECs and ovarian macrophages from bovine CL.
Phenotypes
PCO (polycystic ovarian syndrome)
Mutations
2 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: fertile Comment:De Felipe et al. (1998) disrupted the NK1 receptor gene in mice. Mutant mice were healthy and fertile, but the
characteristic amplification ('wind-up') and intensity coding of nociceptive reflexes were absent.
Species: mouse
Mutation name: None
type: null mutation fertility: fertile Comment: Increased formation of corpora lutea in neurokinin 1-receptor deficient mice by Loffler S,et al Mol. Reprod. Dev. 68: 408-414, 2004 .
There is evidence to suggest that the tachykinin-receptor system may be involved in female reproduction. Recently, we have shown that the mRNA transcripts of the preprotachykinin-A which encodes substance P (SP), a member of the tachykinin family, and of NK1-R (preferred receptor of SP) are expressed in the bovine corpus luteum (CL) of early developmental stage. The question arises whether the system is expressed at the protein level and influences the ovulatory process and CL formation. For this reason, ovaries from a mouse mutant in which the NK1-R gene had been disrupted were studied. By using RT-PCR, mRNA expression of NK1-R was confirmed in both the ovary and the uterus of wild-type mice. Weaning frequency and litter size, as recorded over 6 months, were similar in both groups. However, counting of CL in serial paraffin sections revealed a significant higher number of CL in the NK1-R deficient mice in comparison to the wild-type group (P < 0.01). The increased formation of CL in NK1-R deficient mice corresponded to a considerable number of CL with retained oocyte not found in ovaries of the wild-type group. We conclude: The CL with a retained oocyte may indicate that the muscular apparatus of the preovulatory follicle plays a role in oocyte expulsion and that contractility of the follicle wall is deficient in the mutant group. Our observation may have implications for the luteinized unruptured follicle syndrome in humans.