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)

We have previously demonstrated that the in vivo vitreal injection of an antisense oligonucleotide directed to the kinesin heavy chain inhibits retinal kinesin synthesis by 82% and concomitantly inhibits rapid transport of total protein into the optic nerve by 70%. These results establish a major role for kinesin in rapid axonal transport in vivo. Recently, the cloning of a family of kinesin-like molecules from the mammalian brain has been reported, and some of these proteins are also expressed in neurons. To assign to specific function to the kinesin heavy chain we inhibited the kinesin synthesis with an antisense kinesin oligonucleotide and assessed the axonal transport into the optic nerve of representative proteins from each of three vesicle classes that contain rapidly transported proteins. Marker proteins used were substance P for peptide-containing synaptic vesicles, the amyloid protein for plasma membrane precursor vesicles, and several integral synaptic vesicle proteins. Our results indicate that the major anterograde motor protein for all three vesicle classes utilizes kinesin heavy chain, although we discuss alternative explanations.
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PMID:Inhibition of kinesin synthesis in vivo inhibits the rapid transport of representative proteins for three transport vesicle classes into the axon. 753 13

The amyloid protein (beta A4) is found in the CNS of patients with Alzheimer's disease; however, the pathogenic role of this protein is not known. In the present study, a peptide fragment of beta A4 (beta A4 25-35; Gly-Ser-Asn-Lys-Gly-Ala-Ile-Ile-Gly-Leu-Met-NH2), which contains the conserved C-terminal sequence of substance P (X-Gly-Leu-Met-NH2), and the neuropeptide substance P (SP) were examined for their ability to modulate nicotine-evoked secretion from cultured bovine adrenal chromaffin cells. Secretion of the released endogenous catecholamines was monitored by electrochemical detection after separation by HPLC. Secretion induced by 10(-5) M nicotine was inhibited by SP and beta A4 25-35. The IC50 of SP and beta A4 25-35 was 3 x 10(-6) and 3 x 10(-5) M, respectively. SP and beta A4 25-35 both protected against nicotine receptor desensitization. However, beta A4 25-35 was approximately 10-fold less effective than SP in its protective effect. The present work shows that beta A4 25-35 can mimic the modulatory actions of SP on the nicotinic response of cultured bovine chromaffin cells, i.e., inhibition of the nicotinic response and protection against nicotinic desensitization. These modulatory actions may be associated with changes in nicotinic receptor levels reported to occur in Alzheimer's disease.
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PMID:An amyloid peptide, beta A4 25-35, mimics the function of substance P on modulation of nicotine-evoked secretion and desensitization in cultured bovine adrenal chromaffin cells. 767 24

Ginsenoside Rb1 (Rb1), a saponin of North American ginseng (Panax quinquefolium L.), has been found to exert beneficial effects on memory and learning, putatively through its actions on the cholinergic system. In situ hybridization studies show that Rb1 increases the expression of choline acetyltransferase and trkA mRNAs in the basal forebrain and nerve growth factor mRNA in the hippocampus. Other neurotrophins (brain-derived neurotrophic factor, neurotrophin-3), genes encoding neuropeptides (preproenkephalin, preprotachykinin) and amyloid protein precursor were also studied, but no significant change was observed. These findings support the specificity of the effects of Rb1 on certain aspects of the cholinergic and neurotrophic systems.
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PMID:Ginsenoside Rb1 regulates ChAT, NGF and trkA mRNA expression in the rat brain. 922 15

Alzheimer's beta amyloid protein (A beta) is a 39 to 43 amino acid peptide that is a major component in the neuritic plaques of Alzheimer's disease (AD). The assemblies constituted from residues 25-35 (A beta 25-35), which is a sequence homologous to the tachykinin or neurokinin class of neuropeptides, are neurotoxic. We used X-ray diffraction and electron microscopy to investigate the structure of the assemblies formed by A beta 25-35 peptides and of various length sequences therein, and of tachykinin-like analogues. Most solubilized peptides after subsequent drying produced diffraction patterns characteristic of beta-sheet structure. Moreover, the peptides A beta 31-35 (Ile-Ile-Gly-Leu-Met) and tachykinin analogue A beta(Phe(31))31-35 (Phe-Ile-Gly-Leu-Met) gave powder diffraction patterns to 2.8A Bragg spacing. The observed reflections were indexed by an orthogonal unit cell having dimensions of a=9.36 A, b=15.83 A, and c=20.10 A for the native A beta 31-35 peptide, and a=9.46 A, b=16.22 A, and c=11.06 A for the peptide having the Ile31Phe substitution. The initial model was a beta strand where the hydrogen bonding, chain, and intersheet directions were placed along the a, b, and c axes. An atomic model was fit to the electron density distribution, and subsequent refinement resulted in R factors of 0.27 and 0.26, respectively. Both peptides showed a reverse turn at Gly33 which results in intramolecular hydrogen bonding between the antiparallel chains. Based on previous reports that antagonists for the tachykinin substance P require a reverse turn, and that A beta is cytotoxic when it is oligomeric or fibrillar, we propose that the tachykinin-like A beta 31-35 domain is a turn exposed at the A beta oligomer surface where it could interact with the ligand-binding site of the tachykinin G-protein-coupled receptor.
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PMID:Assemblies of Alzheimer's peptides A beta 25-35 and A beta 31-35: reverse-turn conformation and side-chain interactions revealed by X-ray diffraction. 1261 42