The tachykinins are a family of amidated neuropeptides that share a carboxy-terminal sequence
Phe-X-Gly-Leu-Met-NH2 and are found in both vertebrates and invertebrates. The 3 known tachykinins in man are
encoded by 2 genes. One gene encodes a precursor containing both substance P and neurokinin A, while the other
encodes a precursor containing only neurokinin B. (Neurokinin A was formerly known as substance K.)
NCBI Summary:
This gene encodes four products of the tachykinin peptide hormone family, substance P and neurokinin A, as well as the related peptides, neuropeptide K and neuropeptide gamma. These hormones are thought to function as neurotransmitters which interact with nerve receptors and smooth muscle cells. They are known to induce behavioral responses and function as vasodilators and secretagogues. Substance P is an antimicrobial peptide with antibacterial and antifungal properties. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2014]
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.
A novel biological role of tachykinins as an upregulator of oocyte growth: identification of an evolutionary origin of tachykinergic functions in the ovary of the ascidian, Ciona intestinalis. Aoyama M et al. Tachykinins (TKs) and their receptors have been shown to be expressed in the mammalian ovary. However, the biological roles of ovarian TKs have yet to be verified. Ci-TK-I and Ci-TK-R, characterized from the protochordate (ascidian), Ciona intestinalis, are prototypes of vertebrate TKs and their receptors. In the present study, we show a novel biological function of TKs as an inducible factor for oocyte growth using C. intestinalis as a model organism. Immunostaining demonstrated the specific expression of Ci-TK-R in test cells residing in oocytes at the vitellogenic stage. DNA microarray and real-time PCR revealed that Ci-TK-I induced gene expression of several proteases including cathepsin D, chymotrypsin, and carboxypeptidase B1 in the ovary. The enzymatic activities of these proteases in the ovary were also shown to be enhanced by Ci-TK-I. Of particular significance is that the treatment of Ciona oocytes with Ci-TK-I resulted in progression of growth from the vitellogenic stage to the postvitellogenic stage. The Ci-TK-I-induced oocyte growth was blocked by a TK antagonist or by protease inhibitors. These results led to the conclusion that Ci-TK-I enhances growth of the vitellogenic oocytes via upregulation of gene expression and enzymatic activities of the proteases. This is the first clarification of the biological roles of TKs in the ovary and the underlying essential molecular mechanism. Furthermore, considering the phylogenetic position of ascidians as basal chordates, we suggest that the novel TK-regulated oocyte growth is an 'evolutionary origin' of the tachykinergic functions in the ovary.
Expression regulated by
LH
Comment
Tachykinins in the normal and gonadotropin-stimulated ovary of the mouse Debeljuk L. .
In this investigation, substance P (SP) and neurokinin A (NKA) concentrations have been determined in the ovary of control prepubertal mice, and prepubertal mice injected with pregnant mare serum (PMS) gonadotropin, an equine gonadotropin with predominant FSH action, or with PMS followed by human chorionic gonadotropin (hCG), which produces heavily luteinized ovaries after the stimulation with PMS. Control animals were injected with saline. The ovaries of animals treated with gonadotropins were heavier than the control ovaries, the combination of PMS plus hCG produced significantly heavier ovaries than PMS alone. The concentrations of SP and NKA in the ovaries of the animals treated with PMS or PMS/hCG were significantly lower than in control ovaries. No significant differences in ovarian tachykinin concentrations were observed between PMS and PMS/hCG-treated animals. The total ovarian content of SP was lower in PMS-injected animals as compared with the controls. The total ovarian content of NKA was not significantly different in the three groups of animals studied. These results show that ovaries stimulated with gonadotropins have lower concentrations of tachykinins than normal ovaries at the same age. It is therefore evident that gonadotropins can affect tachykinin stores in the ovaries of mice.
Ovarian localization
Cumulus, Granulosa, Luteal cells, neuron
Comment
Expression of Tachykinins and Tachykinin Receptors and Interaction with Kisspeptin in Human Granulosa and Cumulus Cells. Garcia-Ortega J et al. (2016) The neurokinin B/NK3 receptor (NK3R) and kisspeptin/kisspeptin receptor (KISS1R), two systems which are essential for reproduction, are co-expressed in human mural granulosa (MGC) and cumulus cells (CCs). However, little is known about the presence of other members of the tachykinin family in the human ovary. In the present study, we analysed the expression of substance P (SP), hemokinin-1 (HK-1), the NK1 receptor (NK1R) and the NK2 receptor (NK2R) in MGCs and CCs collected from pre-ovulatory follicles of oocyte donors at the time of oocyte retrieval. RT-PCR, quantitative real-time PCR, immunocytochemistry and western blot were used investigate the pattern of expression of tachykinin and tachykinin receptor mRNAs and proteins and the possible interaction between the tachykinin family and kisspeptin. Intracellular free Ca(2+) levels, Ca(2+)]i, in MGCs after exposure to SP or kisspeptin in the presence of SP were also measured. We found that SP, HK-1, the truncated NK1R isoform, NK1R-Tr, and NK2R were all expressed in MGCs and CCs. NK1R-Tr mRNA and NK2R mRNA and protein levels were higher in MGCs, in comparison with CCs from the same patients. Treatment of cells with kisspeptin modulated the expression of HK-1, NK3R and KISS1R mRNAs while treatment with SP regulated kisspeptin mRNA levels and reduced the [Ca(2+)]i response produced by kisspeptin. These data demonstrate that the whole tachykinin system is expressed and acts in coordination with kisspeptin to regulate granulosa cell function in the human ovary.//////////////////
[Ojeda SR, et al 1985 reported evidence for the existence of substance P in the prepubertal rat ovary. The presence of substance P (SP) in the immature rat ovary was determined by
radioimmunoassay (RIA) of acidic extracts. The extracts produced an
inhibition-displacement curve of 125I-SP binding parallel to that generated by
authentic SP in the SP RIA. Initial chromatographic characterization of ovarian SP
in Sephadex G-25 revealed the presence of a molecular form that coeluted with
authentic SP and a more abundant component that eluted earlier, suggesting the
presence of a heavier peptide, immunologically similar to SP.
Majewski M, et al 1996 reported that galanin, substance P and calcitonin gene-related peptide are colocalized in some
afferent neurons innervating the porcine ovary.
Debeljuk L. 2005 reviewed Tachykinins and ovarian function in mammals.
Tachykinins are bioactive peptides whose presence has been demonstrated in endocrine glands, where they likely exert a paracrine modulatory activity on hormonal secretions. In the ovary, tachykinins have been shown to be present in nerve fibers, blood vessels, and in granulosa, luteal and interstitial cells. Tachykinin gene expression was shown in granulosa and luteal cells. Tachykinins have also been found in the follicular fluid. Substance P (SP) has been demonstrated to significantly affect the release of hormonal steroids by ovarian cells in vitro. While some authors found that SP stimulated the release of steroids, others found an inhibitory effect by the same tachykinin. Gonadotropins decrease tachykinin concentrations in the ovary. The neonatal treatment of rats with capsaicin, a drug that depletes SP in primary afferent neurons, resulted in a modest reduction in the reproductive success in rats. The experimental results listed in this review suggest that tachykinins are synthesized in the ovary, in the granulosa and luteal cells. Tachykinins are likely intraovarian modulators of the secretion of hormonal steroids. Their stores in the ovary are likely regulated by pituitary gonadotropins.
Follicle stages
Antral, Preovulatory, Corpus luteum
Comment
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
luteum of early developmental stage.
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.