Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Stress is known to induce abortions, but underlying mechanisms are unknown. Both alloimmunization and injection of antibody to the asialoGM1 determinant of natural killer cells have been shown to prevent stress-triggered abortion in mice. DBA/2J-mated CBA/J female mice were used to investigate the influence of stress during early gestation on systemic hormone levels and on cytokines in the decidua that are thought to be relevant to abortion in nonstress-related murine abortion. Lowered levels of progesterone did not occur as a result of stress. In stressed mice, increased levels of the abortogenic cytokine tumor necrosis factor alpha (TNF alpha) were associated with decreased levels of pregnancy-protective transforming growth factor beta 2-related suppressive activity in uterine decidua. In the alloimmunized animals where stress failed to boost the abortion rate, these effects were abrogated. Production of TNF alpha may be stimulated by the neurotransmitter substance P (SP); after injection of an SP receptor antagonist or SP-antibody, stress failed to increase the abortion rate above the background level. The increased levels of TNF alpha we observed in the stressed animals were completely abrogated in the animals that had received the SP receptor antagonist; stress also failed to decrease the pregnancy-protective suppressive activity in the decidua of these animals. The data indicate that stress may inhibit protective suppressor mechanisms and promote secretion of abortogenic cytokines such as TNF alpha via neurotransmitter SP.
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PMID:Stress-induced murine abortion associated with substance P-dependent alteration in cytokines in maternal uterine decidua. 854 75

The embryo expresses paternal antigens foreign to the mother and therefore has been viewed as an allograft. The maternal immune system responds to paternal antigens on the "graft", and these responses are thought to protect pregnancy. However, pregnancy can be aborted by stress, which stimulates local production of TNF-alpha and inhibits TGF-beta 2-producing natural suppressor cell (NS) activity via a neurotransmitter substance P-dependent pathway. Immunization protects against stress-triggered abortion and CD8+ T cells appear to be required. The objective of the present study was to investigate the importance of CD8+ T cells in the prevention of stress-triggered abortion by immunization. Injection of anti-CD8 increased the abortion rate in nonimmunized mice and in immunized mice. Following anti-CD8 injection, stress failed to further increase the abortion rate; a similar high rate of abortion was seen in immunized and anti-CD8-injected mice. These data suggested that stress could act by neutralization and/or elimination of immunoprotective CD8+ T cell function. CD8+ T cells from pregnant mice have been reported to produce a 34-kDa suppressor factor, but we detected a 1.5- to 2-kDa suppressive factor in the HPLC fractions of supernatants obtained from nonstressed decidua, and this activity was abolished by stress and boosted by immunization with Balb/c cells.
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PMID:Inhibition of immunoprotective CD8+ T cells as a basis for stress-triggered substance P-mediated abortion in mice. 880 91

We review the actions of mammalian tachykinins on uterine smooth muscle. Derived from sensory neurones and non-neuronal cells within the female reproductive tract, tachykinins are potent uterotonic agents. Three tachykinin receptor genes, and the gene encoding neprilysin, the enzyme that inactivates tachykinins, are present in rat, mouse and human myometrium. In rat and human, the tachykinin NK(2) receptor is important in mediating the uterotonic effects of tachykinins; actions at this receptor remain relatively stable or vary only slightly in the face of changing hormonal and gestational status. In contrast, ovarian steroids and pregnancy regulate expression of the tachykinin NK(3), and to a lesser extent, the tachykinin NK(1) receptor, as well as the activity of neprilysin. In the oestrogen primed mouse uterus, the tachykinin NK(1) receptor primarily mediates tachykinin uterotonic effects, but there is a switch to the tachykinin NK(2) receptor by late pregnancy. The possible physiological and pathological roles of tachykinins, including hemokinins and endokinins, in normal and premature labour, stress-induced abortion and menstrual disorders are briefly discussed.
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PMID:Mammalian tachykinins and uterine smooth muscle: the challenge escalates. 1546 17

In a well-established murine abortion model, stress is thought to trigger fetal rejection by inducing a proinflammatory immune response via substance P (SP), being tumour necrosis factor (TNF)-alpha-producing CD8+ T cells involved. Interestingly, the SP metabolite SP5-11 also binds to SP receptors and mediates SP-like effects on immune cells at sites of inflammation. No data were available regarding the effects of SP5-11 on pregnancy outcome in the CBA/J x DBA/2J abortion-prone combination. We investigated the influence of SP5-11 in contrast to stress or SP on the abortion rate and the cytokine production by lymphocytes as well as on the levels of CD8+ T cells. Stress and SP boosted the abortion rate and increased the percentage of type 1 [TNF-alpha, interferon-gamma, interleukin (IL)-12] and type 2 (IL-4 and IL-10) cytokine-producing lymphocytes in blood and decidua, predominantly CD8+ T cells. Interestingly, SP5-11 did not significantly affect the abortion rate or cytokine production in the decidua, while increasing the Th1 and Th2 cytokine production systemically. Our data suggest that stress and SP induce abortion by augmenting the local levels of TNF-alpha, which seems therefore to be a potent trigger of miscarriage. On the contrary, the SP metabolite SP5-11 only affects the systemic cytokine production without boosting the abortion rate in this experimental model.
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PMID:Stress and substance P but not the substance P-metabolite SP5-11 trigger murine abortion by augmenting TNF-alpha levels at the feto-maternal interface. 1639

Until a short time ago, the view prevailed worldwide that children were less sensitive to pain than adults, and such operations as circumcision were performed in babies without adequate anesthesia or analgesia. This view is now considered a misconception, as psychophysiological and behavioral studies show that even neonates have a well-functioning nociceptive system. Nociception generally refers to the neural and sensory aspects of pain, which do not necessarily include conscious experience. There is no discontinuity in the development of the nervous system during birth, and therefore it can be concluded that the fetus is also responsive to noxious stimuli. The question arises as to the stage of ontogeny of the human at which nociceptive behavior begins. Literature on the fetal nervous system reveals that the first signs of somatosensory system function occur at week 7 of gestation and at week 22 the synaptic connection from the nervous periphery to the somatosensory cortex is becoming established. During this period, motor behavior matures, from stereotyped reflexes to spontaneously generated complex motor patterns reminiscent of the repertory of voluntary movement. From week 22 onward the electroencephalogram (EEG) shows increasingly more varied patterns, and sleep-wake states can be discerned after week 30 of gestation. Somatosensory evoked cortial potentials have been recorded from gestational week 28 onward. Substance P, a neuropeptide associated with pain in the adult nervous system, is present in the fetal spinal cord as early as week 12 of gestation, while the antinociceptive opioid peptide enkephalin does not appear until week 24. From week 15 onward, opioid peptides such as beta-endorphin appear in the pituitary; their release becomes sensitive to environmental stimuli from about week 20 onward, which can be considered the onset of pituitary stress responses. In particular, parturition and abortion induced the release of opioid peptides. Studies of conditioned behavior show that the fetus has the ability to learn. It has been hypothesized that the fetus and neonate possess a procedural memory, which is not transferred to the language-based memory of later phases of life. Learning and memory are the most essential elements for the construct of "consciousness." Therefore, a primitive type or level of consciousness might exist in the fetus. Thus, a considerable range of sensorimotor function, including memory, develops during fetal life. Anatomical, physiological and behavioral data suggest that the nociceptive system is included in this development. Although we cannot be sure at present whether the fetus consciously experiences pain, beyond the protective nociceptive behavioral responses, anesthesia should be used for invasive procedures to protect the fetus and its nervous systems.
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PMID:[Pain in the fetus: neurobiological, psychophysiological and behavioral aspects.]. 1841 86

Nerve growth factor (NGF), the first identified member of the family of neurotrophins, is thought to play a critical role in the initiation of the decidual response in stress-challenged pregnant mice. However, the contribution of this pathway to physiological events during the establishment and maintenance of pregnancy remains largely elusive. Using NGF depletion and supplementation strategies alternatively, in this study, we demonstrated that a successful pregnancy is sensitive to disturbances in NGF levels in mice. Treatment with NGF further boosted fetal loss rates in the high-abortion rate CBA/J x DBA/2J mouse model by amplifying a local inflammatory response through recruitment of NGF-expressing immune cells, increased decidual innervation with substance P(+) nerve fibres and a Th1 cytokine shift. Similarly, treatment with a NGF-neutralising antibody in BALB/c-mated CBA/J mice, a normal-pregnancy model, also induced abortions associated with increased infiltration of tropomyosin kinase receptor A-expressing NK cells to the decidua. Importantly, in neither of the models, pregnancy loss was associated with defective ovarian function, angiogenesis or placental development. We further demonstrated that spontaneous abortion in humans is associated with up-regulated synthesis and an aberrant distribution of NGF in placental tissue. Thus, a local threshold of NGF expression seems to be necessary to ensure maternal tolerance in healthy pregnancies, but when surpassed may result in fetal rejection due to exacerbated inflammation.
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PMID:Balanced levels of nerve growth factor are required for normal pregnancy progression. 2482 9