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)

The production of substance P and the mRNA encoding its precursor (preprotachykinin, PPT) is regulated by nerve growth factor (NGF) in dorsal root ganglion (drg) neurons. To explore the mechanism by which NGF regulates the production of PPT mRNA, we have transfected PC12 cells and F11 cells with plasmids containing the bovine PPT promoter linked to the reporter gene chloramphenicol acetyltransferase (CAT). We have identified (i) functional elements within the PPT promoter which are necessary for expression in the absence of NGF and (ii) two separate regions, each of approximately 250 bp, which confer NGF responsiveness. Both regions contained a sequence element, similar to a known transcription factor binding site, which is present in several other NGF-regulated genes.
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PMID:Identification of nerve growth factor-responsive sequences within the 5' region of the bovine preprotachykinin gene. 174 55

Tachykinins and CGRP label two distinct populations of neurons innervating the digestive system: intrinsic and extrinsic, afferents. The bulk of SP/tachykinin innervation originates from intrinsic neurons, even though a minor component of this innervation derives from afferent neurons, which are mostly located in dorsal root ganglia. Afferent SP/tachykinin fibers are mainly confined to a perivascular location and to the submocosa in the gut, but are distributed also to the hepatobiliary pathway and pancreas. On the contrary, the extrinsic CGRP-containing afferents form a major component of the sensory innervation of the alimentary tract, including the rich CGRP innervation of the esophagus, stomach, hepatobiliary tract, pancreas, and vasculature, as well as a portion of non-vascular fibers distributed to the intestinal wall. Tachykinin and CGRP immunoreactivities appear to be colocalized in a population of nerve fibers, which are likely to be extrinsic, afferent, since colocalization of these peptide immunoreactivities has not been reported in intrinsic neurons. The presence of SP/NKA-encoding transcripts in the enteric nervous system and sensory ganglia and the lack of hybridization signal with RNA probes complementary to NKB mRNA indicate that the PPT I gene, but not the PPT II gene, is transcribed in these structures. This observation, along with receptor binding sites and radioimmunoassay data, which have failed to detect NKB receptor binding sites or immunoreactivity (Eysselein et al., 1990; Maggio, 1988; Mantyh et al., 1988; 1989) in the intestine of several mammals, is consistent with a differential expression of the two PPT genes in the periphery and in the central nervous system (Brecha et al., 1989; Warden and Young, 1988). A differential expression of the tachykinin-encoding genes, the existence of multiple tachykinin receptor subtypes (Mantyh et al., 1988; 1989), and the findings that tachykinins can be differentiated on the basis of the potency of their activities (Galligan et al., 1987; Maggio, 1988), support the possibility that each tachykinin is expressed in separate, and perhaps functionally distinct neuronal systems. alpha- and beta-CGRP genes also are differentially expressed according to the neuronal populations: alpha-CGRP mRNA is the most prominent form in sensory ganglia, and beta-CGRP mRNA is the only form detected in enteric neurons (Mulderry et al., 1988; Sternini and Anderson, 1990). In addition, distinct distributions of mRNAs generated from the two CGRP genes have been reported in the central nervous system (Amara et al., 1985). The differential expression patterns of alpha- and beta-CGRP mRNAs are consistent with a differential regulation of the alpha- and beta-CGRP genes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Tachykinin and calcitonin gene-related peptide immunoreactivities and mRNAs in the mammalian enteric nervous system and sensory ganglia. 195 Jul 91

The content and nature of the preprotachykinin (PPT; i.e., substance P/neurokinin A-encoding) messenger RNAs (mRNAs) present in rat brain striatum and limbic tissues were determined by RNA protection experiments. The rank order of PPT mRNA concentration was striatum greater than nucleus accumbens much greater than bed nucleus of the stria terminalis greater than hypothalamus, amygdala and septum. The proportion of beta-(full length) to gamma-(minus exon 4) PPT mRNA was invariant (40/60) among the tissues tested. Because these brain regions receive prominent dopaminergic innervations, the effects of repeated treatment with dopamine antagonists (antipsychotic drugs) on PPT gene expression were assessed. The prototypical dopamine antagonists haloperidol and chlorpromazine decreased striatal PPT mRNA, had no effect on PPT mRNA in the nucleus accumbens or bed nucleus of the stria terminalis, and increased septal PPT mRNA levels. In contrast, the atypical antipsychotic drugs clozapine and l-sulpiride did not alter striatal or septal PPT mRNA, but increased PPT mRNA content in the nucleus accumbens and bed nucleus. The correlation between the effects of typical and atypical antipsychotic drugs on rat striatal and limbic PPT gene expression and their clinical side effects and therapeutic efficacy is discussed.
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PMID:Tachykinin gene expression in rat limbic nuclei: modulation by dopamine antagonists. 197 1

The effects of gamma-preprotachykinin-(72-92)-peptide amide [gamma-PPT-(72-92)-NH2] on salivation in the rat were investigated and were compared with salivation responses elicited by a variety of other tachykinin and related peptides. On intravenous injection or continuous infusion, gamma-PPT-(72-92)-NH2, a naturally occurring N-terminally extended derivative of neurokinin A (NKA), potently stimulated salivation. The rank order of potency of peptides that stimulated salivation was: NPK greater than gamma-PPT-(72-92)-NH2 greater than substance P greater than NKA = Asp-Ala-NKA. Moreover, gamma-PPT-(72-92)-NH2, like NPK, potentiated the effects of substance P on salivary secretion. These results indicate that the actions of gamma-PPT-(72-92)-NH2 may be pharmacologically or physiologically relevant in the actions of tachykinin peptides.
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PMID:gamma-Preprotachykinin-(72-92)-peptide amide potentiates substance P-induced salivation. 247 May 99

Oligonucleotide probes complementary to alpha-tubulin, preprotachykinin A (PPT A), preprosomatostatin (PPSOM), and preproarginine-vasopressin (PPAVP) mRNA were hybridized to sections of rat and rabbit brain and dorsal root ganglia (DRG) at all spinal levels. Approximately 100% of the DRG neurons in the rat and rabbit express alpha-tubulin mRNA, 20-30% express PPT A mRNA and 5-17% express PPSOM mRNA. Whereas neurons which express PPSOM mRNA are of relative uniform size, the neurons which express PPT A mRNA segregate into two broad groups. One group is composed of smaller neurons (200-2,000 microns 2) which contain an extremely dense concentration of PPT A mRNA. The second group is composed of larger neurons (2,000-3,500 microns 2) which contain a moderate concentration of PPT A mRNA. PPAVP mRNA is present in very high concentrations in the paraventricular and supraoptic nucleus of the rat hypothalamus but is not detected in any DRG neurons. In both the rat and the rabbit the density of PPT A and PPSOM mRNA is high in individual DRG neurons in comparison to PPT A and PPSOM mRNA levels contained in most forebrain neurons. These results suggest that although the level of neuropeptide present in DRG neurons is relatively low in comparison to other brain areas, the rate of sensory neuropeptide synthesis and turnover, as reflected by mRNA content, is extremely high.
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PMID:High levels of mRNA coding for substance P, somatostatin and alpha-tubulin are expressed by rat and rabbit dorsal root ganglia neurons. 248 65

In situ hybridisation detection of mRNAs using riboprobes has become a widely used technique. However, the identification of cells producing closely-related yet distinct mRNAs is difficult with the usual size probes. Moreover, it is not always easy to obtain the required cDNA essential for cRNA probe synthesis. To avoid these problems, we have used synthetic oligodeoxynucleotides to generate short, single stranded RNA probes ("oligo-riboprobes"). These probes can be labelled to very high (10(9) cpm/micrograms) specific activity and can be prepared for any published nucleotide sequence. We have used these probes to localise beta (preprotachykinin) PPT mRNA producing neurons in rat hypothalamus and bowel. The results were compared to that obtained with cRNA probes generated from beta preprotachykinin cDNA.
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PMID:Oligo-riboprobes. Tools for in situ hybridisation. 317 Feb 68

Sequence analysis of bovine cDNAs has shown that the biosynthetic precursors of the tachykinins (alpha-, beta- and gamma-preprotachykinins) contain a common amino acid sequence [AYERSVMQDYERRRK] in the C-terminal flanking region. Using an antiserum raised against the synthetic peptide [YERSVMQDYE] in a specific radioimmunoassay, preprotachykinin C-terminal flanking peptide (C-PPT)-like immunoreactivity was measured in extracts of bovine corpus striatum, cerebral cortex and small intestine in concentrations that were equimolar with substance P. Consistent with the presence of two amino acid substitutions in the C-terminal flanking region of human and rat preprotachykinins, the antiserum did not detect immunoreactivity in extracts of human and rat tissues. Chromatographic analysis of the extracts identified two major immunoreactive components. It is proposed that they represent the 16-amino acid residue C-terminal flanking peptide derived from beta- and gamma-preprotachykinins and the 37-amino acid residue C-terminal flanking peptide derived from alpha-preprotachykinin. Treatment of tissue extracts with carboxypeptidase B did not result in a change in C-PPT-like immunoreactivity or in a change in chromatographic properties of the C-terminal flanking peptides suggesting that the C-terminal basic tetrapeptide (RRRK) had already been removed from the primary transcript of the preprotachykinin mRNAs by the action of endogenous processing enzymes.
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PMID:Measurement and partial characterization of the C-terminal flanking peptides from bovine preprotachykinins in extracts of brain and gut. 340 99

The nucleotide sequence of cDNA encoding the human substance P precursor, beta-preprotachykinin (beta-PPT), has been determined. The source of mRNA was a human laryngeal carcinoid tumour that contained a high concentration of immunoreactive substance P. The human beta-PPT polypeptide is 129 amino acids long and contains regions encoding substance P and neurokinin A, each flanked by basic amino acid residues. Residues 72-107 of the human beta-PPT polypeptide encode the sequence of neuropeptide K, an N-terminally extended form of neurokinin A recently isolated from porcine brain.
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PMID:cDNA sequence of human beta-preprotachykinin, the common precursor to substance P and neurokinin A. 377 Feb 10

Rats with streptozotocin-induced diabetes of 4 to 6 weeks duration showed a depletion of both substance P (P < 0.01) and calcitonin gene-related peptide (P < 0.01) in the sciatic nerve. Since expression of both peptides is sensitive to nerve growth factor (NGF) in vitro we examined the effect of treatment of diabetic rats with NGF, which significantly increased the levels of both peptides in treated diabetic animals (P < 0.01 for both). Treatment of non-diabetic rats with a similar NGF regime raised the mean peptide levels to a value similar to that seen in treated diabetic rats but the change was not statistically significant. In vehicle-treated diabetic rats the depletions of sciatic nerve neuropeptides were accompanied by a significant (P < 0.05) reduction in the level of CGRP mRNA in the 4th and 5th lumbar dorsal root ganglia, this was accompanied by an analogous reduction in the mRNA for gamma-preprotachykinin A (gamma-PPT), which did not attain statistical significance. Treatment of diabetic rats with NGF also prevented the deficits in the levels of CGRP and gamma-PPT mRNA in the lumbar dorsal root ganglia (P < 0.05). Treatment of other diabetic rats with the related neurotrophin, brain-derived neurotrophic factor (BDNF), had no effect on the levels of substance P and calcitonin gene-related peptide in the sciatic nerve.
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PMID:Expression of neuropeptides in experimental diabetes; effects of treatment with nerve growth factor or brain-derived neurotrophic factor. 751 41

Three different isoforms of preprotachykinin mRNA (PPT mRNA) encode for substance P and related neuropeptides (1). Here we report a fourth isoform of PPT mRNA which is generated by alternative exclusion of exon-7 and exon-6 from the PPT mRNA. It was present mainly in ileal smooth muscle and mucosa, colon, heart and brain and low level of this mRNA was detected in the jejunal smooth muscle and mucosa. This was not detected in the kidney or uterus. The level of this PPT mRNA was enhanced significantly by 60% during colitis in rat induced by trinitro benzene sulphonic acid.
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PMID:Fourth isoform of preprotachykinin messenger RNA encoding for substance P in the rat intestine. 751 24


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