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)

In the present study, we have re-examined the heterogeneous nature of intrastriatal striatal transplants derived from embryonic day 14-15 rat striatal primordia implanted into the previously excitotoxically lesioned striatum of adult rats, using in situ hybridization histochemistry to localize neurotransmitter-related messenger RNAs. These grafts are characterized by discrete patches of DARPP-32 messenger RNA expression, which cover approximately one-third of the cross-sectional graft area. The messenger RNAs encoding for preproenkephalin (the enkephalin precursor), preprotachykinin (precursor to substance P), choline acetyltransferase, as well as the D1 and D2 dopamine receptors, which are abundant in the normal striatum, were all present in the striatal grafts and were expressed almost exclusively in the DARPP-32-positive graft regions. In these graft regions, the expression of the neurotransmitter-related messenger RNAs was generally similar to that seen in the intact striatum, although the level of expression of preproenkephalin and preprotachykinin messenger RNAs varied notably among the patches of expression. Cellular analysis performed on individual patches showed that the expression per cell of preproenkephalin and preprotachykinin messenger RNAs was inversely related, such that patches with higher than normal preproenkephalin messenger RNA levels displayed lower than normal preprotachykinin messenger RNA levels, and vice versa. Moreover, messenger RNA expression for the dopamine D2 receptor was overall lower than that for the dopamine D1 receptor, both with respect to the level per cell and the number of positive cells within the DARPP-32 patches. Glutamate decarboxylase messenger RNA was expressed throughout the grafts, in 98% of all neurons located in the DARPP-32-positive regions and in 75% of all neurons in the non-DARPP-32 regions of the graft. Interestingly, the cellular expression of glutamate decarboxylase messenger RNA was considerably higher in the non-DARPP-32 expressing regions than that in the DARPP-32 messenger RNA-rich areas, where it approximated that of the intact striatum. Furthermore, grafted neurons located outside the DARPP-32-expressing regions displayed similar levels of expression to those found in the overlying cortex and in the closely adjacent globus pallidus. To further characterize the DARPP and non-DARPP graft compartments, messenger RNAs encoding the alpha 1 and beta 2 subunits of the GABAA receptor were studied. These receptor subunits, which exhibit a high expression in the host cortex and pallidum but little in the intact striatum, were found in discrete patches situated outside, but often closely associated with, the DARPP-32-rich areas of the graft.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neurotransmitter-related gene expression in intrastriatal striatal transplants--I. Phenotypical characterization of striatal and non-striatal graft regions. 770 3

Neuropeptidergic systems have been studied in human tissues and fluids, which include the pituitary and lumbar cerebrospinal fluid, respectively. This paper reviews the qualitative and quantitative mass spectrometric analytical data obtained from three areas of study. Methionine enkephalin (ME) and beta-endorphin (BE) were quantified in the human pituitary by liquid secondary ion mass spectrometry (LSI MS)-tandem mass spectrometry. Corresponding stable isotope-incorporated synthetic peptide internal standards were used. Proenkephalin A and proopiomelanocortin produce ME and BE, respectively. The analysis of neuropeptides in macroadenomas demonstrated a decrease in both of those neuropeptidergic systems relative to controls. An analysis of prolactin-secreting microadenomas showed an increase in the proenkephalin A system. Mass spectrometry was also used to detect opioid peptide-containing proteins in the pituitary. Enzymes that process the precursors of proenkephalin A and tachykinin (substance P) neuropeptides were studied in human lumbar cerebrospinal fluid. Electrospray ionization mass spectrometry was used to characterize the molecular mass of each peptide product.
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PMID:Mass spectrometric analysis of neuropeptidergic systems in the human pituitary and cerebrospinal fluid. 1049 85

We developed a primate model of striatonigral degeneration (SND), the neuropathology underlying levodopa-unresponsive parkinsonism associated with multiple systemic atrophy (MSA-P), by sequential systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 3-nitropropionic acid (3NP) in a Macaca fascicularis monkey. L-Dopa-responsive parkinsonian features emerged after MPTP injections. Subsequent chronic 3NP administration aggravated the motor symptoms and abolished the L-dopa response. In vivo magnetic resonance imaging revealed bilateral striatal lesions. Histopathologically, there was severe dopaminergic cell loss in the substantia nigra pars compacta compared with the control monkey. Furthermore, we observed circumscribed areas of severe neuronal degeneration in the motor striatum. These changes were absent in the control monkey, and they were associated with diffuse metabolic failure as demonstrated by cytochrome oxidase histochemistry. The striatal pathology predominantly involved output pre-pro-enkephalin A- and substance P-containing cells, whereas somatostatin (NADPH-diaphorase)-containing interneurons were relatively spared. Our model therefore reproduced levodopa-unresponsive parkinsonism and SND-like pathologic changes characteristic of MSA-P. The double-lesion primate model of SND may serve as a preclinical test-bed for the evaluation of novel therapeutic strategies in MSA-P.
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PMID:Toward a primate model of L-dopa-unresponsive parkinsonism mimicking striatonigral degeneration. 1083 Apr 20

The presence of tyrosine hydroxylase, neuropeptide Y, vasoactive intestinal polypeptide, galanin, Met-enkephalin-Arg-Gly-Leu, substance P and calcitonin gene-related peptide was studied with immunohistochemistry in uterus-innervating neurones found in the inferior mesenteric ganglia after fluorescent tracer (Fast Blue) injection into different regions of the porcine uterus (uterine cervix, paracervical, middle and paraoviductal part of the uterine horn). Virtually all Fast Blue-positive neurones found in the inferior mesenteric ganglia after tracer injection into all studied parts of the uterus contained tyrosine hydroxylase and ca. 45% of them contained neuropeptide Y. Single galanin-positive/Fast Blue-positive cells were found in the ganglia only after tracer injections into uterine cervix. No other studied substances were found in the Fast-Blue positive neurones of the inferior mesenteric ganglia.
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PMID:Uterus-innervating neurones in porcine inferior mesenteric ganglion: an immunohistochemical characteristic. 1282 1

Midregional Proenkephalin A (MR-PENK A) and N-terminal Protachykinin A (NT-PTA) are stable fragments of the precursor peptides for enkephalins and substance P, respectively. We measured MR-PENK A and NT-PTA concentrations by sensitive chemiluminescence immunoassays in cerebrospinal fluid (CSF) of 19 neurologically healthy controls (NHC), 28 patients with other neurologic disorders (OND), 70 patients with dementia disorders (38 Alzheimer's disease [AD], 8 dementia with Lewy bodies [DLB], 12 frontotemporal dementia [FTD], and 12 patients with vascular dementia [VD]), and 16 patients with acute neuroinflammation (AN). Median concentrations of NT-PTA were decreased in all patient groups compared to NHC showing significant differences between patients with NHC and AN (p<0.001), OND and AN (p<0.001), FTD and AN (p<0.01) and pAD and AN (p<0.05). Median MR-PENK A levels were lower in patients with OND, dementia disorders (including AD, FTD, DLB and VD) and AN compared to NHC subjects, although this differences did not reach statistical significance (p>0.05). A maximum difference of both proneuropeptide fragments was found between NHC subjects and patients with AN, with a more than 2fold decrease in median NT-PTA and a 1.5fold decrease in median MR-PENK A levels. Concentrations of both proneuropeptide fragments were positively correlated in all patients (r=0.77, p<0.001). Our results indicate alterations of the cerebral PENK A- and PTA-system in both, dementia and acute neuroinflammatory disorders. These neuropeptide systems seem to be highly correlated in healthy and pathological status.
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PMID:Midregional Proenkephalin A and N-terminal Protachykinin A are decreased in the cerebrospinal fluid of patients with dementia disorders and acute neuroinflammation. 2020 19


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