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

The influence of deprivation of the neurotransmitter dopamine (DA) on the development of [Met5]-enkephalin (ME) and substance P (SP) neuropeptide systems of the striatum was investigated in Sprague-Dawley rats. The neurotoxin 6-hydroxydopamine (6-OHDA) was used to induce DA deficiency on postnatal day 3 in rats, and the animals were killed at different postnatal time points until 35 days of age. The levels of ME and SP were determined by radioimmunoassay, and the abundance of preproenkephalin (PPE) and preprotachykinin (PPT) mRNA in the striatum was assessed by Northern blot hybridization analysis. The concentrations of DA, 5-hydroxytryptamine (5-HT), and their acid metabolites were determined by HPLC with electrochemical detection. The postnatal development of the PPE-derived peptide ME and the PPT-derived peptide SP closely paralleled the appearance of the respective mRNAs coding for these peptides. The dopaminergic lesion with 6-OHDA led to a marked depletion of DA and its metabolites but produced an increase in content of 5-HT and its metabolite in the striatum. The lesion did not affect the ME and PPE mRNA levels in the striatum up to 25 days but increased the levels at 35 days. In contrast, a decreased developmental expression in SP and PPT mRNA was observed throughout the observation period. The lesion failed to influence the development of the mRNA coding for the structural protein beta-actin. The results indicate that the normal development of enkephalin, tachykinin, and 5-HT systems of the striatum is dependent on the availability of DA, the integrity of dopaminergic neurons, or both. The studies provide evidence for an interrelationship and interdependence between the development of neurotransmitter and neuropeptide systems. It is suggested that an early developmental abnormality in the DA system could permanently alter the neuropeptide systems, which in turn could influence the progression and expression of the DA-deficiency state parkinsonism, Lesch-Nyhan disease, or both.
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PMID:Dopamine-dependent postnatal development of enkephalin and tachykinin neurons of rat basal ganglia. 170 36

Substance P (SP) and other related tachykinins such as neurokinin B (NKB) have been studied widely as mediators of sensory information. The release of SP into the dorsal horn of the spinal cord is increased during nociception, and SP activates nociception-specific dorsal horn neurons. The tachykinin NKB has antinociceptive effects in the spinal cord and is contained in intrinsic spinal neurons; thus, NKB may also contribute to the processing of sensory information. Both neurokinin-1 (NK-1) and neurokinin-3 (NK-3) receptors have been localized in the superficial laminae of the dorsal horn. This study investigated changes in NK-1 and NK-3 receptor mRNA expression during nociception. Following injection of either formalin or complete Freund's adjuvant (CFA) into one hindpaw, the levels of expression of NK-1 and NK-3 mRNAs in the spinal cord dorsal horn and preprotachykinin (PPT) mRNA expression in the lumbar dorsal root ganglia (DRG) were quantitated using solution hybridization-nuclease protection assays. Peptide and receptor mRNA expression levels were normalized to beta-actin mRNA levels, which did not change during the treatments. Formalin (2 or 6 hr) or CFA (4 d) injection produced approximately a twofold increase in SP-encoding PPT mRNA expression in the ipsilateral lumbar DRG. Increased activity in primary afferent neurons containing SP may stimulate the production of SP precursors, providing substrate for increased SP production, release, and turnover in the dorsal horn and periphery.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:NK-1 and NK-3 type tachykinin receptor mRNA expression in the rat spinal cord dorsal horn is increased during adjuvant or formalin-induced nociception. 830 59

In this study, expressions of cell-cycle-related genes: p53, retinoblastoma (Rb), p21, bcl-2(alpha), bcl-2(beta); protooncogene c-ski; glial cell marker protein gene S100beta; neurotransmitter gene, substance P and sexual-differentiation-related genes, androgen receptor (AR) and estrogen receptor beta (ER(beta)), are studied in the olfactory bulb of groups of both six female and six male rats at the ages of 3, 10, 20 and 40 days. Expressions of housekeeping genes such as beta-actin, cyclophilin and proliferating cell nuclear antigens (PCNA) are determined using reverse transcription polymerase chain reaction (RT-PCR) for the correction of unequal amount of cDNA added into the samples. Using labeled 32P-dCTP and Phosphorimager technology, relative abundance of radioactivities of the PCR products is obtained by dividing the radioactivity of each individual sample by the corresponding radioactivities of different housekeeping genes. Data evaluated by Two-way ANOVA indicate that only the bcl-2(alpha) gene expression is affected significantly by age, sex and their interactions no matter which of the three housekeeping genes is used for correction. When beta-actin was used for corrections, effects of age but not sex were found in the expressions of p53, Rb, p21, AR, ER(beta), substance P and S100beta genes, but not in bcl-2(beta), c-ski, cyclophilin and PCNA genes. While cyclophilin was used for corrections, only the p53, Rb, AR, ER(beta), substance P and S100beta but not the bcl-2(beta), p21, c-ski, PCNA and beta-actin genes are affected by age. They are all not influenced by sex of the animals. Only the AR, ER(beta) and S100beta genes are age-dependent when PCNA was used for the correction. The other gene expressions are not altered by sex, while the interactions of age and sex were found to be significantly affecting the bcl-2(beta) gene expression. Conclusively, developmental changes of the p53, Rb, AR, ER(beta), substance P and S100beta genes expressions are quite evidenced while only the bcl-2(alpha) gene seems to change significantly during the sexual differentiation of olfactory bulb in rats.
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PMID:Gene expressions during the development and sexual differentiation of the olfactory bulb in rats. 1067 68

We investigated the effects of PACAP treatment, and endogenous PACAP deficiency, on infarct volume, neurological function, and the cerebrocortical transcriptional response in a mouse model of stroke, middle cerebral artery occlusion (MCAO). PACAP-38 administered i.v. or i.c.v. 1 h after MCAO significantly reduced infarct volume, and ameliorated functional motor deficits measured 24 h later in wild-type mice. Infarct volumes and neurological deficits (walking faults) were both greater in PACAP-deficient than in wild-type mice, but treatment with PACAP reduced lesion volume and neurological deficits in PACAP-deficient mice to the same level of improvement as in wild-type mice. A 35,546-clone mouse cDNA microarray was used to investigate cortical transcriptional changes associated with cerebral ischemia in wild-type and PACAP-deficient mice, and with PACAP treatment after MCAO in wild-type mice. 229 known (named) transcripts were increased (228) or decreased (1) in abundance at least 50% following cerebral ischemia in wild-type mice. 49 transcripts were significantly up-regulated only at 1 h post-MCAO (acute response transcripts), 142 were up-regulated only at 24 h post-MCAO (delayed response transcripts) and 37 transcripts were up-regulated at both times (sustained response transcripts). More than half of these are transcripts not previously reported to be altered in ischemia. A larger percentage of genes up-regulated at 24 hr than at 1 hr required endogenous PACAP, suggesting a more prominent role for PACAP in later response to injury than in the initial response. This is consistent with a neuroprotective role for PACAP in late response to injury, i.e., even when administered 1 hr or more after MCAO. Putative injury effector transcripts regulated by PACAP include beta-actin, midline 2, and metallothionein 1. Potential neuroprotective transcripts include several demonstrated to be PACAP-regulated in other contexts. Prominent among these were transcripts encoding the PACAP-regulated gene Ier3, and the neuropeptides enkephalin, substance P (tachykinin 1), and neurotensin.
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PMID:Neuroprotection by endogenous and exogenous PACAP following stroke. 1702 94

Substance P (SP) is a neuropeptide engaged in the signal transmission of neural C fibers afferents in the myocardium. The actions of SP in the heart are extensive and they are mediated by the neurokinin 1 receptor (NK1R), a member of the tachykinin subfamily of G-protein coupled receptors. The receptors have been found in the heart, but to our knowledge, their exact localization in the heart has not been described yet. Here, we investigated the presence of NK1R protein in separate rat heart compartments by means of western blot and its tissue distribution by means of immunofluorescence. Specificity of NK1R immunolabeling was controlled by preabsorption of the antiserum with its corresponding peptide. Additionally, we investigated abundance of gene for NK1R in separated heart chambers by means of quantitative real-time PCR (RT-PCR). Relative abundance of NK1R mRNA was expressed as a ratio of target gene Cq value to Cq value of control gene - beta-actin. Finally, we studied abundance of NK1R mRNA in different cell types of heart isolated by laser capture microdissection. Immunofluorescence showed NK1R immunoreactivity on the surface of some intracardiac neurons and smooth muscle cells of coronary vessels. The results of quantitative RT-PCR indicate abundance of mRNA for NK1R in all heart chambers with highest level in the left atrium. The presence of NK1R mRNA was detected in some samples of dissected intracardiac neurons, but not in cardiomyocytes or smooth muscle cells of coronary vessels. In the course of long-term diabetes, a significant downregulation of the NK1R mRNA was seen in the right atrium and upregulation in the right ventricle 53 weeks after the induction of diabetes. Our results indicate localization of NK1R in some intracardiac neurons and smooth muscle cells. Impaired transcription of the NK1R gene in the diabetic heart may be induced by unidentified genes or factors involved in the development of diabetic cardiomyopathy.
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PMID:Substance P Receptor in the Rat Heart and Regulation of Its Expression in Long-Term Diabetes. 3005 56