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)

Neuropeptides are sufficiently stable to allow valid radioimmunoassay of peptide concentrations in post-mortem human nervous tissue and in human cerebrospinal fluid. Studies have now documented abnormalities of peptide concentrations in degenerative diseases of the brain. Somatostatin concentration is reduced in the hippocampus and neocortex of patients dying with Alzheimer's type dementia. In Huntington's disease, there are reduced concentrations of substance P, met-enkephalin and cholecystokinin in the basal ganglia; in contrast the concentrations of somatostatin and TRH are increased. Immunocytochemical and experimental lesion studies are underway in an attempt to localize the peptide-containing cells affected by these disorders; and the potential role of alterations in neuropeptide function in the pathogenesis, clinical manifestations and therapy of these illnesses is of great interest. Although alterations of CSF peptide concentrations have been reported in a variety of human diseases, interpretation of these results requires knowledge of the origin and disposition of CSF peptides. Future research into the pathology of peptidergic systems will depend on the development of specific peptide antagonists to probe dynamic aspects of peptide function and on the application of the tools of molecular biology, such as specific mRNA assays, to human material.
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PMID:Implications of neuropeptides in neurological diseases. 620 11

125I-angiotensin II (125I-AII) binding was examined in the hypothalamic-thalamic-septal-midbrain (HTSM) region of HLA-Wistar rats in the presence of CNS-active agents. Angiotensin I, II, and III and saralasin competed for 125 I-AII binding, whereas structurally unrelated peptides such as arginine and lysine vasopressin, oxytocin, LHRH, TRH, bradykinin, and substance P did not. In contrast, ACTH and neurotensin exhibited a weak, dose-dependent competition for 125 I-AII binding. The relative potencies of AII, AI, neurotensin and ACTH were 100:1:0.1:0.05, respectively. Neurotensin and ACTH competition was not additive with AII suggesting interaction at shared binding sites. Most importantly, a wide variety of other CNS active agents such as methyldopa, naloxone, catecholamines, clondidine, and reserpine, failed to inhibit 125 I-AII binding, thus further defining the specificity of the CNS AII receptor.
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PMID:The specificity of angiotensin II receptor binding in rat brain. 627 72

Prolyl endopeptidase (E.C. 3.4.21.26) an enzyme previously called post proline cleaving enzyme, TRH-deamidase or kininase B, may play a role in neuropeptide metabolism. This enzyme, highly active in brain and other tissues, catabolizes proline-containing peptides such as substance P, neurotensin, luteinizing hormone-releasing hormone, thyrotropin releasing hormone, bradykinin and angiotensin II. The structure of beta-neo-endorphin suggests that this opioid peptide is formed by the action of prolyl endopeptidase on a precursor of higher molecular weight. Formation of two biologically active fragments of substance P also requires the action of this enzyme. This review summarizes the current knowledge of the biochemistry of this enzyme, and its potential significance for neuropeptide physiology and pharmacology.
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PMID:Prolyl endopeptidase. 635 55

A variety of neuropeptides, such as TRH, somatostatin, VIP, Substance P, neurotensin, CCK, gastrin, and opioid peptides, alter secretion of GH and PRL from the pituitary. These actions differ according to the route of administration or with experimental conditions, especially anesthesia. Among these peptides, the most consistent results have been obtained with opioid peptides, which stimulate GH and PRL release. Both beta-endorphin and enkephalins are capable of stimulating GH and PRL release in anesthetized and unanesthetized, freely moving rats. The effect is blocked by naloxone, an opiate receptor antagonist. GH secretion induced by opioid peptides seems to be mediated by an alpha-adrenergic mechanism, since treatment with DDC and fusaric acid, which are dopamine-beta-hydroxylase inhibitors, reserpine, and phenoxybenzamine which is an alpha-adrenergic blocking agent, blunted GH secretion. However, pimozide, a dopamine receptor antagonist, and propranolol, a beta-adrenergic blocking agent, were without effect. On the other hand, basal PRL secretion was augmented by pimozide, suggesting the possible involvement of dopamine. It is also possible that serotonin is involved in the GH and PRL release induced by opioid peptides. The physiological significance of opioid peptides in regulating GH and PRL secretion is still unclear. Contradictory results (12,25) have been obtained concerning the effect of naloxone on basal or stimulated GH and PRL secretion in rats, monkeys and humans when tested by the continuous blood sampling method, which rules out the erroneous evaluation of results caused by episodicity of plasma hormone levels. Further studies should clarify the physiological role of opioid peptides in regulating pituitary function.
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PMID:Effect of CNS peptides on hypothalamic regulation of pituitary secretion. 701 Sep 47

Figure 11 summarizes our present understanding of the relationships between the bag cells, the atrial gland, their respective peptides, the central nervous system, and reproductive behavior. There are some interesting aspects of the overall organization of the system. The three hormonal peptides (ELH and the two atrial gland peptides) have specific actions on the central nervous system not unlike what we are currently learning from mammalian systems (e.g., LHRH and TRH). ELH, in addition, has several specific peripheral targets, the details of which remain to be worked out. The fact that ELH and other hormones have multiple targets within the central nervous system as well as nonnervous peripheral targets raises the question of whether one or more different receptors exist for single hormone. We suggest that peptides larger than perhaps five residues may carry several "messages" or receptor binding sites encoded within the one molecule. Large peptides such as ELH could obviously have separate domains of charge distribution within the molecule, and these would have the advantage, over the classical small molecule transmitters, of activating a variety of very different targets. The atrial gland is a peripheral source of peptides with potent nervous system actions; this is reminiscent of peptides in mammals, e.g., substance P, gastrin, and somatostatin, all of which were initially isolated from the gut and which are now being found in and also have actions on the central nervous system. Such resemblances in the principles of organization between mammals and molluscs are constant reminders that neuropeptidergic systems are old tricks in the evolutionary bag and that what we learn from molluscs and other invertebrates about mechanisms and organization will likely apply to mammals.
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PMID:Peptides controlling behavior in Aplysia. 741 70

Subpopulations of raphe pallidus (Rpa) and raphe obscurus (Rob) neurons containing TRH, serotonin (5-HT), and substance P contribute projections to the dorsal vagal complex (DVC). Activation of Rpa and Rob neurons induces a vagal cholinergic-dependent stimulation of gastric secretory and motor function and modulates resistance of the gastric mucosa to gastric injury in rats and cats. The caudal raphe nuclei-DVC pathways containing TRH/5-HT are involved in mediating cold-induced vagal stimulation of gastric function and erosion formation. These results suggest that Rpa/Rob-DVC projections containing TRH/5-HT may be an important pathways in the medullary regulation of vagal activity to the viscera.
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PMID:Caudal raphe-dorsal vagal complex peptidergic projections: role in gastric vagal control. 754 64

In order to test the possible effects of an intravenous administration of substance P (SP) on basal and TRH-stimulated PRL release, SP was infused alone (0.5 or 1.5 pmol/kg-1/min-1 for 60 min) or after TRH (20 or 400 micrograms in an i.v. bolus) in 21 normal male subjects. In addition, plasma cortisol levels during SP infusion were measured. In agreement with previous findings, a significant increase in plasma cortisol levels was observed when the higher (1.5 pmol/kg-1/min-1) but not the lower (0.5 pmol/kg-1/min-1) amount of SP was given. In contrast, basal and TRH (20 or 400 micrograms)-induced PRL release were not modified by SP at any tested amount. These data suggest that, in normal men, plasma SP is not involved in the control of PRL release at the anterior pituitary level.
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PMID:Intravenously infused substance P is unable to change basal and TRH-stimulated PRL secretion in normal men. 769 3

Substance P and the two other mammalian tachykinins, neurokinin A and B, are accepted to have direct regulating effects at the anterior pituitary level. We have examined the effects of substance P (SP) and neurokinin B (NKB), alone and in combination, on prolactin release from cultured anterior pituitary cells grown on collagen-coated micro beads and placed in a perfusion system. Prolactin (Prl) secretion was observed within 25 s after exposure to either secretagogue and reached a maximum within 60-80 s. Furthermore, the prolactin response induced by SP and NKB was dose-dependent. Prl secretion remained constant for up to 4 h when SP or NKB were perifused and then fell gradually towards basal levels. Simultaneous addition of submaximal concentrations of SP and NKB resulted in an additive response compared with the responses of either secretagogue alone. Continuous (8 h) perifusion with SP did not prevent a normal prolactin response by NKB or TRH. These results indicate that the tachykinins, substance P and neurokinin B, release Prl from perifused female rat anterior pituitary cells by interaction with two different receptors, possibly the NK1 and NK3 tachykinin receptor subtypes.
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PMID:Tachykinins induce secretion of prolactin from perifused rat anterior pituitary cells by interactions with two different binding sites. 890 62

Prolyl endopeptidase has been predominantly described as a cytosolic activity capable of cleaving a number of important neuropeptides (including TRH, LHRH, Bradykinin, Angiotensin, Substance P, Neurotensin, Oxytocin and Vasopressin) on the carboxy side of proline. In this paper, we report, for the first time, on the complete purification and characterization of a membrane-bound form of prolyl endopeptidase. This novel activity has been isolated from the synaptosomal (plasma membranes) membranes of bovine brain. Following gel filtration, hydroxylapatite and hydrophobic interaction chromatographies, the prolyl endopeptidase activity was purified 1400-fold with a 23% recovery of activity. The enzyme was shown to have a relative molecular mass of 87 kDa and a Km of 60 microM for its specific fluorimetric substrate, Z-GlyProMCA. The purified enzyme demonstrated a relatively broad substrate specificity and a relatively high affinity for proline-containing neuropeptides. It was shown to be inhibited by certain thiol-protease inhibitors and by the metal chelator, 1,10-phenanthroline, thus possibly classifying it as a 'thimet' activity. The purified particular form of proyl endopeptidase displayed a similar substrate specificity to the previously reported cytosolic forms of the enzyme. However, there were differences between the two forms in term of their sensitivity to inhibitors, their affinities for the peptide substrates and their relative molecular masses. The different subcellular location (i.e. the synaptosomal membrane) of the particulate prolyl endopeptidase is also of potential physiological significance given that here it is more likely to come in contact with the vesicle-bound neuropeptides than is its cytosolic counterpart.
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PMID:Purification and characterization of a novel membrane-bound form of prolyl endopeptidase from bovine brain. 902 55

Using whole-cell patch-clamp techniques, we show that oligosphere-derived oligodendrocyte progenitor cells (OP) display GABA-, glutamate-, 5-HT-, glycine- and acetylcholine-gated inward currents. When OP differentiate into oligodendrocytes (ODC), the amplitude of peak currents elicited by saturating concentrations of these transmitters decreases except for 5-HT. Intracellular Ca2+ concentration changes induced by microperfusion of glutamate, 5-HT, TRH, met-enkephalin and substance P were monitored using a fluo-3-based calcium imaging system. When OP cells differentiate into ODC, a global decrease of the proportion of responding cells is observed. During type-2 astrocytes commitment, this proportion decreases for 5-HT, TRH- and metenkephalin stimulations whereas it remains constant for substance P and glutamate. These data demonstrate a development regulation of neurotransmitter- and neuropeptide-induced responses within the oligodendroglial lineage.
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PMID:Developmental regulation of neuroligand-induced responses in cultured oligodendroglia. 960 52


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