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)

Several hypothalamic neuropeptides and amino acids are known to inhibit or excite pituitary luteinizing hormone (LH) release, but the precise interplay between these 2 classes of signals in episodic LH discharge is not known. In this study, we have evaluated the interaction between neuropeptides shown previously to inhibit LH release in castrated rats and the excitatory amino acid agonist, N-methyl-D-aspartate (NMDA), on LH release in intact male rats. Rats received a permanent intracerebroventricular (i.c.v.) cannula and 9-12 days later an intrajugular cannula for frequent blood sampling. The next day, rats received i.c.v. either saline (SAL, 3 microliters, controls) or a neuropeptide: the opioid beta-endorphin (beta-END; 2.9 nmol), the tachykinin neuropeptide K (NPK, 2.5 nmol) or the cytokine interleukin-1 beta (IL-1 beta, 5.9 pmol) in SAL. The LH response to 2 consecutive i.v. injections of NMDA (5 mg/kg) at 30 min intervals was evaluated. In control rats, each NMDA injection evoked a significant release of LH at 10 min. Quite unexpectedly, the three peptides, instead of exerting an inhibitory effect, enhanced the LH response to NMDA. The peak plasma LH levels after each NMDA injection and the cumulative LH responses were significantly higher in peptide-treated than in control rats. This peculiar ability of the peptides that inhibit LH release in castrated rats, to potentiate the NMDA-induced LH release in the presence of gonadal steroids was further validated in female rats treated with an opiate receptor agonist, morphine (MOR) which is also known to suppress LH release in ovariectomized rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The hypothalamic peptides, beta-endorphin, neuropeptide K and interleukin-1 beta, and the opiate morphine, enhance the excitatory amino acid-induced LH release under the influence of gonadal steroids. 782 26

Interleukin-1 beta (IL-1 beta) is a pleiotropic cytokine that appears to be an integral component of the bidirectional signalling between the immune and central nervous systems. It is produced in the hypothalamus and has been shown to inhibit the hypothalamo-pituitary-gonadal axis and to activate the hypothalamo-pituitary-adrenal axis. IL-1 beta is reported to up-regulate the tachykinin, substance P (SP), in the peripheral nervous system. We have recently observed that members of the hypothalamic tachykinin family including SP, neurokinin A (NKA) and two N-terminal extended forms of NKA (neuropeptides kappa and gamma), inhibit hypothalamic LHRH and pituitary LH release and stimulate adrenal corticosterone secretion. The similarity in the endocrine effects of the tachykinins and the cytokine prompted us to test the hypothesis that IL-1 beta may stimulate the hypothalamic tachykinins, which would then mediate the neuroendocrine effects of IL-1 beta. First, the effects of IL-1 beta on the in vitro release of NKA-like immunoreactivity (NKA-li) from the hypothalamus was examined. Addition of 10 nM IL-1 beta significantly increased NKA-li release from the hypothalami of castrated rats, but not from the hypothalami of intact rats. To identify the site of IL-1 beta action, the effects of intraventricular IL-1 beta (100 ng) on NKA-li levels in various hypothalamic sites of intact and castrated rats were examined. The results showed that IL-1 beta increased NKA-li selectively in the median eminence (ME) and arcuate nucleus (ARC) of castrated rats only.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of interleukin 1 beta on the hypothalamic tachykinin, neurokinin A. 785 71

The neuropeptides are involved in the immune response and in hormonal homeostasis. In this review, we analyse the interactions between the cytokine, the neuropeptide and the hormonal networks in rheumatoid arthritis (RA). We first consider pituitary-adrenal axis dysfunction in RA. An inappropriate response to cortisol in chronic inflammation has been reported, i.e., a decrease of the corticotropin-releasing-hormone (CRH) secretion by the hypothalamus. In contrast, the immunostimulant hormone prolactin (PRL) is upregulated. PRL is released by the pituitary after stimulation by neuropeptides [serotonin, thyroid-releasing-hormone (TRH), or vasoactive-intestinal-peptide (VIP)], and is down-regulated by pro-inflammatory cytokines (IL-1, IL-6). The decreased testosterone concentration observed in male RA patients is associated with HLA B 15. Thus, an altered sex hormone status and a genetic predisposition are related to HLA antigens, and increase the subject's susceptibility to the development of RA. The terminal C fibres release neurotransmitters such as substance P, neurokinin A and calcitonin-gene-related-peptide (CGRP) within the joints, and contribute to local inflammation, synoviocyte proliferation and collagenase production. The parasympathetic system may attenuate the immune response through the neuropeptide VIP. In contrast, the beta 2 adrenergic fibres of the sympathetic nervous system increase joints degradation in RA. This review presents the currently extensive knowledge regarding the immune-neuro-hormonal network, and its implication in the pathogenesis of RA.
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PMID:Modulation of the immune response by the neuro-endocrine axis in rheumatoid arthritis. 795 11

Maintenance of the integrity of the single-cell-thick intestinal epithelium as an in vivo barrier between environmental Ags and mucosal immunocytes is pivotal for health. The T cell cytokine IFN-gamma consistently disrupts this epithelial barrier in vitro, but the substances in mucosa that may be responsible for sustaining or enhancing barrier function have not been clearly identified. Therefore, we characterized the effect on the epithelial barrier of TGF-beta 1 and three prominent neuropeptides (VIP, substance P, somatostatin) by using a model system in which barrier function of a mature polar human colonic epithelial (T84) cell monolayer is reflected in 1) the electrical potential difference across the apical to basolateral surface of each cell, 2) the transmonolayer permeability to macromolecules such as horseradish peroxidase, and 3) lactate dehydrogenase release into the medium indicating epithelial cell cytolysis. Whereas T84 monolayers exposed to TGF-beta 1 alone demonstrated a modest increase in electrical resistance and barrier integrity, TGF-beta 1 showed a striking ability to reduce the capacity of IFN-gamma to disrupt epithelial barrier function. Characterization studies demonstrated that this TGF-beta 1 effect was prolonged (e.g., days) after a single exposure, progressive over the dose range 0.1 to 2.5 ng/ml, reversible with increased concentrations of IFN-gamma, and more pronounced when TGF-beta 1 exposure was to basolateral rather than to apical epithelial membranes. Macromolecular (horseradish peroxidase) penetration of epithelium was not simultaneously altered by TGF-beta 1 and epithelial cellular injury was minimal as gauged by lactate dehydrogenase release. Additional studies using a human pathogen demonstrated that TGF-beta 1 delayed and decreased the barrier disruption caused by exposure to Cryptosporidium parvum. TGF-beta 1 may be the first of a new class of cytokines that maintains and/or enhances barrier function of human enterocytes, in part by countering the effect of a T cell cytokine.
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PMID:Regulation of intestinal epithelial barrier function by TGF-beta 1. Evidence for its role in abrogating the effect of a T cell cytokine. 798 70

The aim of this study was to demonstrate the effect of intra-articular morphine following knee arthroscopy performed in infiltration analgesia. Fifty-two healthy patients were randomized to receive either 1 mg of morphine or placebo. The pain was assessed 2, 4, 8 and 24 h after the procedure by (1) a VAS scale and (2) the amount of acetaminophen consumed. Demographic data in the 2 groups were similar. The pain scores at 8 and 24 h and the acetaminophen consumption after 8 h were lower in the morphine group (P < 0.05). Our results support the hypothesis of peripherally distributed opioid receptors. Stratifying data in therapeutic versus diagnostic arthroscopy indicated additional effect of morphine in patients undergoing therapy (P < 0.1), an aspect supporting the hypothesis of peripherally administered morphine as a potential suppressor of the substance P-mediated cytokine cascade and the peripheral leukocyte activity. Intra-articular morphine (1 mg) after knee arthroscopy offers efficient analgesia lasting more than 24 h. The method is devoid of side effects and deserves wider recognition.
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PMID:Low-dose intra-articular morphine analgesia in day case knee arthroscopy: a randomized double-blinded prospective study. 800 5

Murine Schistosomiasis mansoni is a parasitic disease in which granulomas develop around the schistosome ova that lodge in the liver and intestines of the host. The granuloma eosinophils make substance P (SP), a cytokine with immunoregulatory properties. Within the granuloma SP can modulate IFN-gamma production through interaction with a substance P-like receptor. SP belongs to a family of hormones called tachykinins. Three mammalian tachykinins are SP, neurokinin A (substance K), and neurokinin B (neuromedin K). In humans and rats, there are at least three distinct tachykinin receptors designated NK-1, NK-2, and NK-3. The NK-1 receptor binds only SP with high affinity. Using reverse transcription-PCR, cDNA cloning, and sequence analysis, we showed that granulomas isolated from the liver of infected mice express an authentic SP (NK-1) receptor but have no detectable neurokinin A (NK-2) and neurokinin B (NK-3) receptor mRNA, as determined by PCR. CD4+ granuloma T lymphocytes, purified by FACS, express NK-1 receptor mRNA. Normal liver devoid of granulomas exhibited none of the three tachykinin receptor subclasses.
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PMID:Molecular evidence that granuloma T lymphocytes in murine schistosomiasis mansoni express an authentic substance P (NK-1) receptor. 812 Mar 92

The purpose of this study was to demonstrate the effect of intra-articular morphine following knee arthroscopy performed in infiltration analgesia. Fifty-two healthy patients were randomized to receive either morphine 1 mg or placebo. The pain was assessed two, five, eight and 24 hours after the procedure by 1) a VAS scale and 2) the amount of acetaminophen consumed. Demographic data in the two groups were similar. The pain scores at eight and 24 hours and the acetaminophen consumption after eight hours were lower in the morphine group (p < 0.05). Our results confirm the hypothesis of peripherally distributed opioid receptors. Stratifying data in therapeutic vs. diagnostic arthroscopy suggests an additional effect of morphine in patients undergoing therapy (0.05 < p < 0.10), an aspect which supports the hypothesis of peripherally administered morphine acting as a potential suppressor of the substance P mediated cytokine cascade. Intraarticular morphine 1 mg after knee arthroscopy offers efficient analgesia lasting more than 24 hours. The method is devoid of side effects and deserves wider recognition.
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PMID:[Analgesic effect of low-dose intra-articular morphine after ambulatory knee arthroscopy]. 827 40

A large body of recent evidence suggests that a number of inhibitory and excitatory neuropeptides and amino acids may participate in the episodic secretion of hypothalamic LHRH and pituitary LH in castrated rats. However, the precise functional relationships among these messenger molecules in the control of LH secretion remain to be ascertained. The aim of this study was to test the hypothesis that inhibition of LH release by an opioid [beta-endorphin (beta END)], cytokine [interleukin-1 beta (IL-1 beta)], or tachykinin [neuropeptide-K (NPK)] is a result of diminished excitatory amino acid (EAA) signaling. Adult male rats were castrated and received an intracerebroventricular cannula in the third ventricle for administration of beta END (10 micrograms/rat), NPK (2.5 nmol/rat), or IL-1 beta (100 ng/rat) 2 weeks postcastration. One day before the experiments, rats received an intraatrial cannula for frequent blood sampling and for iv injection of the glutamate receptor agonist N-methyl-D-aspartate (NMDA; 5 mg/kg) at 30-min intervals. Blood samples for LH measurements were withdrawn immediately before and 10 min after each NMDA injection. The results show that intracerebroventricular beta END, IL-1 beta, or NPK inhibited LH release. Multiple injections of NMDA did not alter the existing pattern of LH secretion in castrated control rats. However, similar NMDA injections completely prevented the decrease in LH release by beta END, IL-1 beta, or NPK. Plasma LH levels in these rats remained within the range seen in untreated control rats throughout the 120-min duration of the experiment, and NMDA injections at 30-min intervals evoked pulses of LH that resembled those seen normally in castrated rats. The blockade of the inhibitory effects of the three peptides by NMDA and previous knowledge of hypothalamic sites of NMDA action suggest that EAA systems may represent a common pathway down-stream in the hypothalamic LHRH-regulating circuitry to mediate diminution of LH release by inhibitory peptides. Further, their inhibitory influence may be exerted either directly at the level of LHRH neurons and/or by diminution in EAA efflux, leading to suppression of LHRH and LH release.
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PMID:Evidence that luteinizing hormone suppression in response to inhibitory neuropeptides, beta-endorphin, interleukin-1 beta, and neuropeptide-K, may involve excitatory amino acids. 831 64

The expression of the alpha 6 beta 4 and alpha 6 beta 1 integrins on epidermal Langerhans cells (LC) before and after mast cell degranulation was studied in cultured human neonatal foreskin by immunohistochemistry. Twenty-four hours after addition of mast cell secretagogues, morphine sulfate, or substance P, solitary mid-epidermal cells showed staining for the integrin subunits alpha 6, beta 4, and beta 1. This expression was not observed in cultured control explants, and immunostained cells were confirmed to be non-epithelial, dendritic cells by immuno-electron microscopy. The identity of these cells as LC was further established by coincident staining for alpha 6 and CD1a using double immunofluorescence labeling. Addition of tumor necrosis factor-alpha (TNF alpha), the predominant cytokine in mast cell granules, also induced LC to express alpha 6 integrins. Furthermore, preincubation of skin organ cultures with anti-TNF alpha antibodies or the mast cell inhibitor cromolyn sodium abrogated the ability to induce alpha 6 integrins on LC consequent to experimental mast cell degranulation by substance P. These data implicate a role for mast cell-derived TNF alpha in the regulation of the integrins alpha 6 beta 4 and alpha 6 beta 1 on LC. These findings may have important implications relevant to mechanisms for spatial localization of LC within the cutaneous compartments during immune responses.
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PMID:Mast cell degranulation upregulates alpha 6 integrins on epidermal Langerhans cells. 834 16

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


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