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)

An enkephalin-degrading aminopeptidase using Leu-enkephalin as a substrate was purified about 4100-fold from guinea pig serum. The purified preparation was apparently homogenous, showing one band on polyacrylamide gel electrophoresis. The molecular weight of the enzyme was approx. 92 000. The aminopeptidase had a pH optimum of 7.0 with Km values of 0.12 mM and 0.18 mM for Leu- and Met-enkephalin, respectively. The enzyme hydrolyzed neutral, basic and aromatic amino acid beta-naphthylamides, but did not the acidic one. The enzyme was inhibited strongly by metal-chelating agents, bestatin and amastatin and weakly by puromycin. Among several biologically active peptides, angiotensin III and substance P strongly inhibited the enzyme.
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PMID:Purification and characterization of an enkephalin-degrading aminopeptidase from guinea pig serum. 636 29

Cathepsin B was purified about 11,000-fold from monkey skeletal muscle by ammonium sulfate fractionation and sequential column chromatographies monitored by assaying of Z-Phe-Arg-MCA hydrolase activity. The purified enzyme gave a single protein band on SDS-polyacrylamide gel electrophoresis, and its molecular weight was estimated to be 24,000 by gel filtration. It had a pH optimum of 6.5, required a thiol reducing agent for activation, and was inhibited by various thiol protease inhibitors. These properties were similar to those reported for cathepsins B from other sources. Although the enzyme scarcely hydrolyzed ordinary proteins, such as casein, hemoglobin, and bovine serum albumin, it degraded myosin and actin among various myofibrillar proteins. These results strongly suggested that skeletal muscle cathepsin B may participate in the degradation of muscle proteins in vivo. In addition, cathepsin B was shown to hydrolyze various neuropeptides such as Leu-enkephalin, beta-neoendorphin, alpha-neoendorphin, dynorphin(1-13), and substance P. It appeared to act on these peptides mainly as a dipeptidyl carboxypeptidase, although not so rigorously, presumably due to its endopeptidase activity.
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PMID:Purification and characterization of cathepsin B from monkey skeletal muscle. 672 39

In an attempt to improve the ultrastructural preservation of tissue immunostained with the postembedding staining technique, we verified the effect of postfixation with OsO4 on the antigenicity of several pituitary hormones and neuropeptides. For this purpose, the rat pituitary and central nervous system (CNS) were perfused with 2.5% glutaraldehyde and postfixed in two different ways: a) postfixation by immersion of small fragments in a mixture of 1% OsO4 and 1% potassium ferrocyanide, and b) postfixation with perfusion of 500 ml of 0.5% OsO4. The results obtained were similar with the two types of postfixation. In the pituitary gland, all the hormones could be very easily detected, although the staining was less intense for the glycoprotidic hormones. In the CNS the following neuropeptides: somatostatin, luteinizing hormone-releasing hormone (LHRH), Leu-enkephalin and substance P could be immunostained. These results indicate that a variety of polypeptidic antigens, including small neuropeptides, can survive postfixation with OsO4. In both the pituitary and CNS, the ultrastructural preservation was very good with a high contrast of membranes, thus permitting a clear identification of positive organelles. Moreover, it appears that, since the synaptic junctions are well-preserved after postfixation with OsO4, postembedding staining can now be utilized to identify and classify the different categories of endings containing neuropeptides.
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PMID:Immunocytochemical detection of peptides in osmicated and plastic-embedded tissue. An electron microscopic study. 701 13

Striatal expression of preproenkephalin and preprotachykinin messenger RNA was studied in normal controls and in patients with Parkinson's disease using in situ hybridization histochemistry. In controls, preproenkephalin messenger RNA was expressed in a population of medium-sized neurons of mean cross-sectional area 165 microns 2, accounting for 66% of striatal medium-sized neurons, whereas preprotachykinin messenger RNA was expressed in a population of medium-sized neurons of mean cross-sectional area 204 microns 2 (23% larger than those expressing enkephalin, P < 0.05), accounting for 58% of medium-sized striatal neurons. Much lower levels of both preproenkephalin messenger RNA and preprotachykinin messenger RNA were expressed by large neurons in the globus pallidus and substantia nigra reticulata. In addition, preproenkephalin messenger RNA was expressed at low levels by neurons in the subthalamic nucleus. In Parkinson's disease cases, there was a statistically significant increase in preproenkephalin messenger RNA expression in the body of the caudate (109% increase, P < 0.05) and in the intermediolateral putamen (55% increase, P < 0.05) due to an increase in the level of gene expression per neuron rather than an increase in the number of neurons expressing preproenkephalin messenger RNA. Similar increases were observed in other putaminal subregions and in the putamen as a whole, but these did not reach statistical significance. No change in preprotachykinin messenger RNA expression was detected. These findings demonstrate selective up-regulation of a striatal neuropeptide system in Parkinson's disease compatible with increased activity of the "indirect" striatopallidal pathway, which is thought to play a crucial role in the pathophysiology of akinesia and rigidity in this condition.
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PMID:Preproenkephalin and preprotachykinin messenger RNA expression in normal human basal ganglia and in Parkinson's disease. 747 78

Bilateral intranigral infusions of three different peptide agonists were made in rats exposed to fluphenazine decanoate, 30 mg/kg/month (FLU) or vehicle (CON) for seven months. Oral movements were monitored repeatedly during the neuroleptic pretreatment period, as well as before the intranigral infusion and during a 90-min period postinfusion. The FLU group had an increased frequency of vacuous chewing movements (VCM) during the pretreatment period in comparison to controls. Intranigral infusion of the neurokinin-1 (NK1) receptor agonist, [Pro9]Substance P (2.5 nmol on each side), 5-7 weeks after the last FLU injection, caused a significant increase of VCM in both pretreatment groups, lasting 7 min after the infusion. The VCM response to [Pro9]Substance P in the FLU group was significantly higher than in the CON group. A NK2 agonist [Lys5, MeLeu9, Nle10]Neurokinin A(4-10) (2.5 nmol) failed to produce significant changes in oral activity. A Leu-enkephalin analogue [D-Ala2,D-Leu5]enkephalin (3.8 nmol) induced a massive biting behavior in both FLU and CON rats. Using VCM as a behavioral assay, an increased nigral sensitivity to a NK1 agonist is demonstrated in rats chronically exposed to neuroleptics. No corresponding alterations could be ascribed for the NK2 receptor agonist or the Leu-enkephalin analogue.
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PMID:Intranigral stimulation of oral movements by [Pro9] substance P, a neurokinin-1 receptor agonist, is enhanced in chronically neuroleptic-treated rats. 750 30

A range of neuropeptides has been identified in the adrenal glands of many mammalian species. In many cases these peptides have been located in nerves supplying the adrenal cortical cells, or within clusters of chromaffin cells within the zona glomerulosa. The function of these neuropeptides has yet to be determined, but from their location within the gland it is clearly possible that they may have a role in the regulation of aldosterone secretion. The effects of Met-enkephalin, Leu-enkephalin, neuropeptide Y, substance P, corticotrophin-releasing hormone (CRH) and neurotensin on aldosterone secretion were investigated using the intact perfused rat adrenal gland in situ. All the peptides tested, except CRH, caused a significant increase in aldosterone secretion over the dose range of 1 pmol to 10nmol, with a maximum response of about a twofold increase in secretion. Met-enkephalin, however, at a dose of 10 nmol caused a 350% increase in aldosterone secretion, a response comparable with that seen in response to angiotensin II in this preparation. These results suggest that, while substance P, neuropeptide Y, neurotensin and Leu-enkephalin all have the capacity to cause modest increases in the rate of steroid secretion by the zona glomerulosa, these neuropeptides probably do not have a major role in the acute regulation of aldosterone secretion, at least under basal conditions. Met-enkephalin, on the other hand, was a more potent stimulus to aldosterone secretion, and thus may have a role in the control of aldosterone secretion.
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PMID:The role of neuropeptides in the regulation of adrenal zona glomerulosa function: effects of substance P, neuropeptide Y, neurotensin, Met-enkephalin, Leu-enkephalin and corticotrophin-releasing hormone on aldosterone secretion in the intact perfused rat adrenal. 751 Nov 55

In the present study, we describe the neurochemical effects of intranigral injections of colchicine in the rat forebrain using immunohistochemistry and in situ hybridization. The observations on the injected side are compared to the contralateral one and to the sham-operated rats. We demonstrate that such injections are able to strongly enhance the immunoreactivity for Met-enkephalin (ME), substance P (SP) and neuropeptide Y (NPY) in numerous nerve cell bodies of the limbic system (injected side), whereas the levels of the corresponding mRNAs are differently modified according to the region examined. A clear correlation between the enhancement of the immunostaining for ME and SP and that of the preproenkephalin (PPA) and preprotachychinin gene transcripts was observed in neuronal perikarya of the medial amygdaloid nucleus (SP), of the dorsolateral hypothalamus (ME) and of the ventromedial hypothalamic nucleus (SP). These observations are interpreted as an induction--or increased expression--of neuropeptide genes in neuronal perikarya postsynaptic to nerve fibers originating in the midbrain and brain stem. In this case, colchicine is thought to block the electrophysiological activity of ascending nerve fibers (anterograde and postsynaptic effect). In the case where the enhancement of the immunoreactivity for the studied neuropeptides was associated with no change or a decreased expression of the corresponding genes in the same brain areas, colchicine may have blocked the axoplasmic transport of peptides in nerve fibers projecting to the midbrain and/or brain stem (6). This may result in a retrograde accumulation of peptides in the nerve cell bodies of origin and, eventually, in a negative feedback regulation of the corresponding encoding genes in these perikarya (retrograde and presynaptic effect of colchicine). The drastic behavioral effects of bilateral intranigral injections of colchicine, on ingestive behavior in particular, have been studied in a following paper.
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PMID:Effects of intranigral injections of colchicine on the expression of some neuropeptides in the rat forebrain: an immunohistochemical and in situ hybridization study. 751 85

We examined the effect of chronic administration (14 days) of haloperidol (2 mg/kg/day) or sulpiride (100 mg/kg/day), on the mRNA levels of various genes in the rat striatum and pituitary by quantitative in situ and Northern blot hybridizations. In the pituitary, haloperidol and sulpiride induced similar increases of mRNAs of pro-opiomelanocortin (POMC) (+65% and +73%), prolactin (PRL) (+821% and +840%) and growth hormone (GH) (+32% and +47%), but sulpiride induced a greater increase of D2R mRNA (+125%) than haloperidol (+92%). In the striatum, sulpiride and haloperidol had different effects: sulpiride induced a higher increase than haloperidol of both preproenkephalin A (PPA) mRNA (+67% versus +47%) and D2 dopamine receptor (D2R) mRNAs (+72% versus +40%). Moreover, haloperidol and sulpiride had opposite effects on substance P (SP) mRNA. Haloperidol decreased the amount of SP mRNA by 20% while sulpiride increased it by 20%. The D1 dopamine receptor (D1R) mRNA level was not significantly modified after either treatment. Our results demonstrate that the effect of a chronic haloperidol treatment on striatal dopamine receptors and neuropeptide mRNA levels is different to that of sulpiride, whereas it is similar on pituitary hormones mRNA levels.
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PMID:Differential influence of haloperidol and sulpiride on dopamine receptors and peptide mRNA levels in the rat striatum and pituitary. 751 29

There is evidence that adrenal blood flow may be regulated in part by neuropeptides released from the capsular region of the adrenal gland in response to splanchnic nerve stimulation. The present study investigated the effects of various neuropeptides on the rate of perfusion medium flow through an intact in situ perfused rat adrenal preparation. Vasoactive intestinal polypeptide (VIP) had the greatest effect, causing a 136% increase in flow at the highest dose used (10 nmol in a 200 microliters bolus). Of the other peptides tested Met-enkephalin caused a 50% increase in flow, and the others (Leu-enkephalin, neurotensin and substance P) had only a minor effect, increasing perfusion medium flow rate by no more than around 35%. Neuropeptide Y, in contrast, caused a significant decrease in perfusion medium flow rate: the maximum effect was a 30% decrease with a dose of 1 nmol in a 200 microliters bolus. The significance of this observation awaits elucidation. It is clear from the actions of the neuropeptides tested that they may have a significant role in the regulation of adrenal blood flow. In view of the findings of other authors: that VIP is released in response to splanchnic nerve stimulation, and that it is specifically localised in the capsular region of the adrenal, it seems most likely that VIP is the major peptide involved in mediating the increased adrenal blood flow following splanchnic nerve stimulation.
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PMID:The role of neuropeptides in the regulation of adrenal vascular tone: effects of vasoactive intestinal polypeptide, substance P, neuropeptide Y, neurotensin, Met-enkephalin, and Leu-enkephalin on perfusion medium flow rate in the intact perfused rat adrenal. 751 3

There is much evidence to suggest that glucocorticoid secretion may be influenced by the splanchnic innervation to the adrenal gland, and that this effect may be mediated by neuropeptides. The present studies investigated the effects of several neuropeptides on corticosterone secretion by the intact perfused rat adrenal gland in situ. Both vasoactive intestinal polypeptide and Met-enkephalin caused a dose-dependent increase in corticosterone secretion, with a maximum response of 450% and 370% increment in corticosterone respectively. Of the other peptides tested, Leu-enkephalin, substance P and neurotensin all stimulated corticosterone secretion, with a maximum response of around 160% increase in each case. Neuropeptide Y on the other hand, had only a minor effect, which was only apparent over a small dose range. These results support the theory that adrenal neuropeptides may have a role in the regulation of glucocorticoid secretion.
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PMID:The role of neuropeptides in the regulation of adrenal zona fasciculata/reticularis function. Effects of vasoactive intestinal polypeptide, substance P, neuropeptide Y, Met- and Leu-enkephalin and neurotensin on corticosterone secretion in the intact perfused rat adrenal gland in situ. 752 79


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