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)

High levels of BN/GRP are present in classic SCLC and lung carcinoids, whereas BN immunoreactivity is absent in variant SCLC, adenocarcinoma, large cell carcinoma, squamous cell carcinoma, and mesothelioma cell lines. BN-like peptides are secreted from classic SCLC into the tissue culture medium. The secretion rate of BN-like peptides from cell line NCI-H345 was increased 3-fold by VIP (1 microM). Also, VIP increased the cAMP levels in cell line NCI-H345 by an order of magnitude. Therefore, SCLC cells have functional VIP receptors which regulate the secretion of BN-like peptides. Also, SRIF (100 nM) inhibits the VIP-stimulated increase in cAMP levels and secretion rate of BN-like peptides from SCLC cells. Because BN stimulates colony formation, VIP and/or SRIF may be able to alter the growth of SCLC cells. BN-like peptides are secreted from SCLC cells into the plasma. The levels of BN immunoreactivity in the plasma of SCLC patients with extensive disease is 2- to 40-fold greater than that of patients with limited disease. Secretin infusion into patients with extensive disease produces a transient increase (7-fold) in the plasma concentration of BN-like peptides. BN-like peptides are also present in the CSF of SCLC patients. When released from SCLC cells, BN-like peptides may interact with cell surface receptors. [Tyr4]BN binds with high affinity (Kd = 0.5 nM) to a single class of sites (1500/cell) on cell line NCI-H345. The carboxyl terminus of BN or GRP is essential for high-affinity binding activity. BN-like peptides elevate cytosolic Ca2+ levels as a result of increased phosphatidylinositol turnover. The putative BN receptor antagonist [D-Arg1, D-Pro2, D-Trp7,9, Leu11]substance P inhibits high-affinity [Tyr4]BN binding, the ability of BN to elevate cytosolic Ca2+ levels, and colony formation of SCLC cells. Therefore, BN receptor antagonists may serve as useful agents to inhibit the growth of SCLC.
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PMID:The release of bombesin-like peptides from small cell lung cancer cells. 285 97

The authors describe the anatomical features and physiological properties of central serotonergic neurons. The central serotonin neurons (part of which store peptides [substance P, TRF, enkephalins] in addition to 5HT) are highly collateralized reticular-type brain stem neurons receiving multi-modal afferent information from ascending sensory and descending motor pathways. They are under control by noradrenergic, peptidergic and and gaba-ergic projection neurons and interneurons. Furthermore, they establish variable synaptoid and synaptic contacts to neuronal, glial and secretory targets throughout the entire neuraxis and send terminal branches into the ventricular CSF space. Firing rate and transmission activity appear to be controlled in a complex and rather rigid manner by 5HT release-dependent dendrodendritic and dendrosomatic inhibition via autoreceptors (which also regulate release at the axon terminals) and via transsynaptic inhibitory feedback circuits which may involve gabaergic projection and interneurons. 3H-imipramine appears to bind to an "imipramine recognition site" in the vicinity of the 5HT carrier, and to a variety of other transport and (postsynaptic) receptor sites (NA uptake, H1, 5HT2- and alpha 1-binding sites). Circumstantial evidence points to an as yet undetermined role of the postsynaptic 5HT-1-binding sites in neurotransmission. 5HT-2-binding sites fulfil the criteria for receptors: binding affinity of antagonists to these sites correlates significantly with their potency to inhibit behavioral excitation in rats elicited by 5-hydroxytryptophan or 5HT agonists.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Anatomical features and physiological properties of central serotonin neurons. 299 53

The onset of therapeutic effectiveness of carbamazepine is generally very rapid in the treatment of seizure and paroxysmal pain disorders, shows some lag in the treatment of mania, and exhibits the longest lag in depression. These time course variations may indicate that different mechanisms underlie the efficacy of carbamazepine in the differential neuropsychiatric syndromes. Biochemical and pharmacological data suggest that the anticonvulsant effects of carbamazepine are related to "peripheral-type" benzodiazepine and alpha 2-noradrenergic receptor systems and to its ability to stabilize sodium channels. GABAB (baclofen-like) actions appear to be involved in antinociceptive, but not anticonvulsant, effects. The relatively acute time course of antimanic efficacy may be related to the above-mentioned mechanisms or to other effects related to systems postulated to be altered in the manic syndrome. These effects might include carbamazepine's ability to increase acetylcholine in the striatum, decrease probenecid-induced levels of CSF homovanillic acid (HVA) in man and dopamine turnover in animals, decrease CSF norepinephrine in manic patients, inhibit adenylate cyclase activity (in response to norepinephrine, dopamine, adenosine, or ouabain), decrease GABA turnover, or act as a vasopressin agonist. Efficacy in depression may be related to actions in man that take time or chronic drug administration to develop, such as increases in plasma tryptophan, decreases in CSF somatostatin, decreases in thyroid indices, and increases in urinary free cortisol excretion and, in animals, increases in substance P sensitivity and increases in brain adenosine receptors. The ability of carbamazepine to block the development of lidocaine- and cocaine-induced seizures also requires chronic administration, suggesting that these seizure models may provide a unique perspective for understanding mechanisms of time-dependent effects.
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PMID:Time course of clinical effects of carbamazepine: implications for mechanisms of action. 328 May 60

In order to clarify the mechanism of the analgesic effect of ceruletide (CRL), the peptides B-endorphin (BE), ACTH, prolactin (PRL), growth hormone (GH) and substance P were determined in the basal state and following IV CRL administration in 11 patients. CRL, at the dose of 2 ng/kg/min, significantly augmented BE levels in the plasma, and in CSF. Substance P levels were significantly augmented by CRL in the plasma, while ACTH levels were significantly augmented in CSF. GH and PRL levels were not affected by CRL. Placebo had no effect on any of the measured peptides. The effect of CRL on mood and anxiety, known to be affected by opioids, was studied in 14 patients with psychogenic headache. The effect of histamine induced headache on State trait anxiety inventory and on Mood adjective check list was studied before and after administration of placebo or CRL. CRL significantly diminished anxiety when compared to placebo. Elation, surgency and egotism were significantly augmented while skepticism was significantly diminished by CRL. The CRL effect on mood and pain may be mediated by augmented levels of neurohormones both in the plasma and in CSF.
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PMID:Effect of ceruletide on pituitary-hypothalamic peptides and on emotion in man. 617 96

Three children, from different kinships, with generalized insensitivity to pain, showed unusual manifestations of congenital, presumably inherited, sensory and autonomic neuropathy. The first child appeared to have a syndrome resembling those previously described as congenital indifference to pain, congenital universal loss of pain sensation from infancy without other apparent neurological deficit. Unlike most types of hereditary sensory and autonomic neuropathies (types I, II, III), but like type IV, she had normal sensory nerve action potentials. Abnormalities of sudomotor function and of somatosensory evoked potentials were demonstrated. A severe decrease in the number of sural nerve A delta fibres and a small reduction in C fibres were demonstrated morphometrically. An abnormality of C fibres was confirmed by a marked reduction in nerve dopamine-beta-hydroxylase activity. The plasma and CSF concentrations of beta endorphins, substance P and several other neuropeptides and hormones were normal. Unequivocal evidence of a neuropathic lesion is provided by this patient; her disorder may be identified as the fifth type of hereditary sensory and autonomic neuropathy. The second patient had a congenital pansensory neuropathy and progressive retinitis pigmentosa. Whether the disorder is inherited and, if so, whether the retinitis pigmentosa results from the same or from a second genetic abnormality, is unclear. The third case has, in addition to what is usually seen in hereditary sensory and autonomic neuropathy, type II, an unusually severe kinaesthetic difficulty in oral food handling. The sural nerves of the second and third patients had fibre composition characteristic of hereditary sensory and autonomic neuropathy, type II, few or no myelinated fibres and reduced numbers of unmyelinated fibres.
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PMID:Not 'indifference to pain' but varieties of hereditary sensory and autonomic neuropathy. 618 47

Methionine-enkephalin, substance P, and homovanillic acid concentrations were measured in the CSF of subjects not affected by neurologic disorders (group 1), and in parkinsonian patients who had a slight or moderate (group 2) or severe (group 3) disability. Homovanillic acid and substance P concentrations in the CSF of groups 2 and 3 were respectively lower and higher than in group 1. On the contrary, an increase in CSF methionine-enkephalin content was found only in group 2. Our results confirm in humans the close relation between the dopaminergic and peptidergic transmissions in the nigrostriatal system that has been observed in experimental animals.
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PMID:Methionine-enkephalin, substance P, and homovanillic acid in the CSF of parkinsonian patients. 619 90

The tissue content of up to eight neuropeptides, viz bombesin (BOM), cholecystokinin (CCK-8), neurotensin (NT), neuropeptide Y (NPY), peptide histidine isoleucine amide (PHI), somatostatin (SRIF), substance P (SP) and vasoactive intestinal polypeptide (VIP), in rat hypothalami removed at various times of the day, was measured using specific radioimmunoassays. There was significant variation in the content of BOM, CCK-8, NT, PHI, SP and VIP across a 24-h period. The levels of BOM, CCK-8 and NT were lowest around the onset of darkness (1900 h) and rose throughout the night to reach a peak around the time of lights on. Hypothalamic content of all eight peptides fell between 0700 h and 1300 h by an average of 45 +/- 4%. Basal release of these peptides, as well as that in the presence of 48 mM potassium (K+), was measured from hypothalami removed between 0700 and 1900 h and incubated in vitro in a CSF-like medium. Basal secretion of NT significantly increased, whilst that of CCK-8 significantly decreased over the same period. There was no significant change in the basal release of the other neuropeptides. The release in the presence of 48 mM K+ of SP decreased significantly during the day, whilst that of VIP significantly increased. There was also a significant change in the stimulated release of BOM, levels falling during the morning and rising again at 1900 h. 48 mM K+ caused a significant increase in the release of SRIF and SP at all times tested. Whilst 48 mM K+ induced a significantly higher release of CCK-8 and NT in the morning, this stimulus was ineffective in the evening. The contrary was true in the case of BOM, NPY and VIP, where a significant stimulation was induced only at 1900 h. The possible implications of these findings are discussed.
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PMID:24-hour variation in content and release of hypothalamic neuropeptides in the rat. 619 15

Using a radioimmunoassay procedure substance P-like activity was measured in samples of human CSF obtained from 12 patients with major depressive disorder, 12 with schizophrenia, and 15 control cases diagnosed as psychiatrically normal. Levels were significantly higher in CSF of patients with depressive disorder as compared with schizophrenic patients or controls. Chemical characterization revealed that the measured activity was less basic than substance P itself and might be due to C-terminal fragments. A component reacting with an antiserum highly specific for the substance P[1-7]fragment was found in CSF of patients with depressive disorder. The results indicate that substance P-related peptides may be biological markers in psychoses, particularly in major depressive disorder.
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PMID:Elevation of substance P-like peptides in the CSF of psychiatric patients. 620 62

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

Macrophages are supposed to play a key role in inflammatory and tumor angiogenesis. Their importance derives from (1) their ubiquitous presence in normal and especially inflamed tissues, (2) their potential to become activated in response to appropriate stimuli, and (3) their repertoire of secretory products. By release of proteases, growth factors (bFGF, GM-CSF, TGF-alpha, IGF-I, PDGF, VEGF/VPF, TGF-beta), and other monokines (IL-1, IL-6, IL-8, TNF-alpha, substance P, prostaglandins, interferons, thrombospondin 1), activated macrophages have the capability to influence each phase of the angiogenic process, such as alterations of the local extracellular matrix, induction of endothelial cells to migrate or proliferate, and inhibition of vascular growth with formation of differentiated capillaries. This review describes macrophage physiology and the influence of macrophage secretory products on the different phases of angiogenesis in vitro and in vivo.
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PMID:Macrophages and angiogenesis. 750 44


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