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)

Preprotachykinin B (PPT-B) contains two peptide sequences which are flanked by pairs of dibasic amino acids: the decapeptide neurokinin B and a 30 amino acid non-tachykinin peptide consisting of the amino acids 50-79 of PPT-B. Whereas the existence of neurokinin B is well established in brain and peripheral tissues, native PPT-B(50-79) has not been identified so far. We have previously studied the distribution of PPT-B(50-79)-immunoreactivity in the rat brain using antibodies directed against synthetic PPT-B(50-79). Now we adapted a radioimmunoassay for characterizing neurochemically PPT-B(50-79)-immunoreactivity in the rat. In the brain concentrations ranging from 2 to 180 fmol/mg wet tissue weight were measured using synthetic PPT-B(50-79) as standard. The highest concentrations were observed in the interpeduncular nucleus and in the hypothalamus (180 and 90 fmol/mg tissue, respectively). Intermediate concentrations (15 to 60 fmol/mg tissue) were present in cortical areas, in the hippocampus, the spinal cord and in the olfactory bulb. Modest levels were detected in the cerebellum. Considerably lower concentrations of PPT-B(50-79)-immunoreactivity were observed in peripheral tissues. They were highest in the adrenal medulla and in the urinary bladder (3.0 and 1.2 fmol/mg tissue, respectively). This distribution, as observed by radioimmunoassay, correlated to that previously revealed by immunocytochemistry. Tissue concentrations of total PPT-B(50-79) immunoreactivity, however, were slightly higher than those of neurokinin B. Gel filtration chromatography on Sephadex G50 and reversed phase HPLC revealed at least three PPT-B(50-79) immunoreactive peaks. About 90% of the PPT-B(50-79)-immunoreactivity was contained within 2 peaks of apparently higher molecular weight than PPT-B(50-79). A minor portion of PPT-B(50-79)-immunoreactivity comigrated with the synthetic peptide, suggesting that only minor amounts of PPT-B(50-79) are formed in vivo. The processing enzyme(s) cleaving protachykinin B at the pair of basic amino acids (Lys80-Arg81) located between PPT-B(50-79) and neurokinin B may not be acting at the Arg48-Arg49 site (followed by -Leu50) at the amino terminal end of PPT-B(50-79).
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PMID:Neurochemical characterization of preprotachykinin B(50-79) immunoreactivity in the rat. 765 92

Experiments were performed to test several predictions of the hypothesis that activity pattern-dependent changes in intracellular free calcium concentration ([Ca2+]i) might play a role in the translation of altered patterns of neuronal activity into changes in neurotransmitter gene expression. It was shown that (1) the Ca2+ channel blocker cadmium prevented depolarization-induced preprotachykinin-I (PPT-I) gene repression in rat sympathetic neurons; (2) the magnitudes of transient rises in [Ca2+]i were dependent upon the pattern in which a fixed number of depolarizing stimuli were delivered; and (3) stimulation at 10 Hz for 24 h did not repress PPT-I mRNA, while the same number of pulses delivered in 0.2 s bursts of 50 Hz caused a highly significant reduction to 30 +/- 2.5% of control levels.
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PMID:Regulation of intracellular calcium and preprotachykinin neurotransmitter precursor gene expression by patterned electrical stimulation in rat sympathetic neurons. 775 90

Tachykinin-immunoreactive neurons are a subgroup of the GABA neuronal population in layer IVC of monkey primary visual cortex. Following brief periods of monocular deprivation in adult monkeys, immunoreactivity for both GABA and tachykinins is dramatically reduced in layer IV cells that lie within the deprived ocular dominance columns of this cortical area. The present study shows that these activity-dependent changes are associated with changes in mRNA levels but over different time courses. Radioactive antisense riboprobes derived from monkey-specific cDNAs were used to localize glutamic acid decarboxylase (GAD) and beta-preprotachykinin (beta PPT) mRNAs by in situ hybridization histochemistry. GAD and beta PPT mRNAs decreased in deprived ocular dominance columns of adult monkeys when neural activity was abolished in one eye by intraocular injections of tetrodotoxin (TTX). beta PPT mRNA levels fell within 5 d of deprivation and thus appeared to parallel the fall in immunodetectable tachykinin levels. By contrast, reduced GAD mRNA levels were detectable only after 15 d of deprivation and long after the fall in immunoreactive GAD and GABA levels has maximized. These results suggest that tachykinin gene expression is regulated by transcriptional mechanisms as part of the first response to reduced neural activity whereas the initial downregulation of immunoreactive GAD and GABA depends on posttranscriptional mechanisms. Following a more prolonged period of deprivation, a secondary mechanism for GAD regulation appears to be engaged at the level of gene transcription or possibly by changes in mRNA stability.
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PMID:Activity-dependent changes in GAD and preprotachykinin mRNAs in visual cortex of adult monkeys. 818 Apr 90

We succeeded in amplifying tachykinin I specific cDNAs from cerebral tissue of guinea pig, rabbit, rat, hamster, trout and tupaia in the expected size range of 820-980 bp. The amplified 859 bp rabbit gamma-preprotachykinin I cDNA was sequenced and consisted of the whole 345 bp gamma-PPT I coding sequence including the substance P and neurokinin A coding regions and a 505 bp large 3'-nontranslated region. Both, molecular weight and sequence comparison emphasizes the very high phylogenetic age of the preprotachykinin I gene.
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PMID:Nucleotide sequence of the rabbit gamma-preprotachykinin I cDNA. 836 93

The serotonergic neurons of the medullary raphe also contain the peptide neurotransmitters substance P (SP) and thyrotropin releasing hormone (TRH). In this study we asked whether the manipulation of serotonin levels alters the levels of mRNA coding for pre-proTRH. Just like the mRNA coding for the precursor of SP (preprotachykinin, PPT), levels of TRH mRNA are increased when serotonin synthesis is inhibited by para-chlorophenylalanine (pCPA) and decreased when serotonin reuptake is blocked by zimelidine. However, subtle differences suggest that the mechanisms behind these changes are different. Levels of TRH mRNA are still decreased after 14 days of zimelidine treatment, a time when levels of PPT mRNA have returned to control values. In addition, the serotonin reuptake blocker fluoxetine lowers levels of TRH but not PPT mRNA. Finally, the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) induces a transient decrease in levels of PPT mRNA similar to that induced by zimelidine, but does not decrease levels of TRH mRNA even when 10-fold higher doses are administered. These results suggest that while some pharmacological manipulations appear to alter TRH and PPT mRNA levels coordinately, the mechanisms regulating the synthesis of these two colocalized neurotransmitters are different.
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PMID:Serotonin modulates the levels of mRNAS coding for thyrotropin-releasing hormone and preprotachykinin by different mechanisms in medullary raphe neurons. 838 58

This study was undertaken to characterize changes in the tachykinin system induced by hyperoxic exposure and the potential effects on airway contractile responses. We exposed 7-day-old rat pups to either room air or hyperoxia (> 95% O2) for 7 days to assess pulmonary beta-preprotachykinin (beta-PPT) gene expression, substance P (SP) levels, and airway contractile responses to cholinergic stimulation before and after neurokinin-1 (NK1) receptor blockade. Lung beta-PPT mRNA expression, lung and tracheal SP levels, and contractile responses to exogenous acetylcholine and electrical field stimulation were measured in vitro in normoxia- and hyperoxia-exposed tracheal cylinders. Hyperoxia caused a 1.1- to 2.6-fold increase in steady-state lung beta-PPT mRNA and a 50 and 32% increase in SP levels of lung and trachea, respectively. In response to cholinergic stimulation, maximal contractile force (Emax) of hyperoxia exposed tracheal muscle was significantly higher than for normoxic controls. Addition of the SP (NK1) receptor blocker CP-99994 (10 microM) decreased sensitivity to electrical field stimulation in both hyperoxic and normoxic trachea without a significant decline in Emax. These data provide evidence for both increased SP production and enhanced maximal contractile responses of hyperoxia-exposed neonatal trachea to cholinergic stimulation. The tachykinin peptide SP does not, however, appear to play a major role in the enhanced airway reactivity associated with hyperoxic lung injury during early postnatal life.
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PMID:Effect of hyperoxia on substance P expression and airway reactivity in the developing lung. 925 38

Two cDNAs, size 969 bp and 1146 bp respectively, encoding goldfish gamma-preprotachykinin (gamma-PPT) were identified. Both cDNAs contain the same 345 bp open reading frame. The deduced 114-amino acid gamma-PPT contains the sequence of substance P, carassin and neurokinin A. sequence analysis of the two cDNA 5'-untranslated regions shows that the two cDNAs may represent different PPT-A gene transcripts resulting from the alternative transcriptional start sites. Expression of gamma-PPT mRNA was detected in a wide range of brain areas from the olfactory bulbs to the posterior brain region, as well as in the intestine, testis and pituitary.
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PMID:Goldfish gamma-preprotachykinin mRNA encodes the neuropeptides substance P, carassin, and neurokinin A. 928 30

Although the tachykinins substance P (SP) and neurokinin A have been largely localized to neurons, eosinophils have also been shown to express these peptides. Our aim was to determine whether rat alveolar macrophages (AM) express preprotachykinin gene-I (PPT-I) mRNA that encodes these tachykinins and to examine expression during inflammation. PPT-I mRNA was detected by reverse transcription (RT)-polymerase chain reaction (PCR) in AM and brain (control) but not in peritoneal macrophages. Northern analysis showed that PPT-I mRNA was induced two- to fourfold by in vivo treatment of rats with intratracheal lipopolysaccharide (LPS) and in vitro after 4 h of exposure to LPS. This increase was inhibited by dexamethasone. In situ RT-PCR and immunocytochemistry further confirmed that AM express PPT-I mRNA and SP-like immunoreactivity, respectively, which was enhanced by LPS treatment. A 1.3-kb transcript consistent with PPT-I mRNA was detected by Northern analysis of bronchoalveolar lavage neutrophils. Therefore, rat AM express PPT-I mRNA that is upregulated in AM by LPS and is attenuated by dexamethasone. PPT-I mRNA was also detected in lung neutrophils.
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PMID:Rat alveolar macrophages express preprotachykinin gene-I mRNA-encoding tachykinins. 937 37

Tachykinins inhibit salt appetite when applied intracranially in a number of brain regions and may function as endogenous inhibitors of sodium intake. To test the hypothesis that induced increases in salt appetite might involve disinhibition via a reduction in endogenous tachykinin expression, we used a semi-quantitative in situ hybridization analysis to investigate changes in brain areas expressing preprotachykinin-A (PPT-A) and preprotachykinin-B (PPT-B) mRNAs of rats after 1 day of sodium depletion (1d Na dep). PPT-A mRNA levels were detected in neurons of the olfactory tubercle (Tu), the nucleus of the olfactory tubercle (LOT), the dorsal and ventral caudate-putamen (d-CPu and v-CPu), the bed nucleus of the stria terminalis (BNST), the medial preoptic area (mPOA), the habenula (Hb) and the postero-dorsal part of the amygdala (MePD). PPT-B mRNA levels were measured in fundus striati (FStr), d-CPu, v-CPu, BNST, mPOA, dorsomedial hypothalamic nucleus (DMD), arcuate nucleus (Arc), central amygdaloid nucleus (CeL), basolateral amygdaloid nucleus (BLV), LOT, Hb and basal nucleus of Meynert (B). 1d Na dep reduced by 33-61% the mean number of PPT-A grains/cell in Tu, LOT, d-CPu, BNST, mPOA, Hb and MePD compared to control animals. Levels of PPT-B mRNA were not reduced as much by 1d Na dep, although statistically significant reductions of 26, 34 and 17% were found in v-CPu, BNST and B, respectively. These findings, therefore, support the hypothesis that endogenous tachykinins exert an inhibitory influence over sodium appetite.
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PMID:In situ hybridization analysis of preprotachykinin-A and -B mRNA levels in short-term sodium depletion. 938 74

This review summarizes the current data regarding the mechanisms by which two mammalian neurokinins (tachykinins), substance P (SP) and neurokinin-A (NK-A) are involved in hematopoiesis. SP and NK-A are derived from the preprotachykinin-I (PPT-I) gene which can be induced by cytokines and neurotrophic factors. In the bone marrow (BM), nerve fibers and stroma are potential sources for the PPT-I gene products. SP and NK-A interact with either of three cloned receptors, neurokinin-1 (NK-1), NK-2 or NK-3, although SP and NK-A exhibit binding preferences for NK-1 and NK-2 respectively. Through specific receptors, SP and NK-A exert dichotomous hematopoietic effects mediated mostly by the BM stroma. SP enhances the proliferation of primitive BM stem cells and progenitors and these effects correlate with the induction of stimulatory hematopoietic growth factors. NK-A appears to be protective to stem cells through the induction of TGF-beta. Proliferation of myeloid progenitors is inhibited by NK-A, effects which correlate with the induction of two suppressive factors, TGF-beta and MIP-1alpha. Stimulation of NK-2 leads to partial blunting of the enhanced stimulatory effects mediated by NK-1. Furthermore, stimulatory hematopoietic cytokines upregulate NK-1 expression and downregulate the constitutively expressed NK-2 in BM stroma. Together, the experimental evidence suggests that NK-A-NK-2 interactions could be a feedback to hematopoietic stimulation. Expression of NK-1 and NK-2 in CD34+ cell lines and also, the presence of SP binding sites on primary CD34+ cells suggest that the neurokinins could be interacting directly with BM progenitors and stem cells. In BM stroma, cytokines and neurokinins regulate the expression of each other and also, their respective receptors. In summary, the current literature pertaining to hematopoietic regulation indicates the involvement of a complex network that includes, but not exclusive of the cytokines and neurokinins. The current models that pertain to stem cell proliferation and differentiation should therefore add neuropeptides to the list of hematopoietic modulators.
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PMID:Hematopoietic regulation mediated by interactions among the neurokinins and cytokines. 949 98


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