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)

The cardiovascular effects of CP-96,345, a non-peptide antagonist of substance P, were analyzed in vivo and in vitro. In the anaesthetized rat, the i.v. injection of 3 mumol kg-1 of CP-96,345 induced a fall in mean arterial blood pressure and a reduction in heart rate. Similar effects were obtained with the enantiomer CP-96,344 (2R,3R)-cis-isomer of CP-96,345) which does not interact with substance P receptors. Both enantiomers, at a concentration of 10 microM, decreased the beating frequency of the isolated atria and of the isolated perfused heart of the guinea-pig to a similar extent, and caused transient coronary dilatation. CP-96,345 (10 microM) decreased the spontaneous sinus rate, prolonged the atrioventricular-nodal conduction interval and the His-bundle conduction interval of the perfused guinea-pig heart. The intraventricular spread of conduction was markedly inhibited. During programmed stimulation 10 min after the beginning of the drug application, the effective refractory periods evaluated by stimulation with premature beats, as well as rate dependent effective refractory periods, of the atrioventricular node, of the atrial and of the ventricular myocardium, were prolonged. Sinus node recovery time was also prolonged. It was concluded that these cardiac effects of CP-96,345 were not caused by an action of the compound on substance P receptors.
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PMID:CP-96,345, a non-peptide antagonist of substance P. III. Cardiovascular effects in mammals unrelated to actions on substance P receptors. 138 36

There are receptors on lymphocytes for substance P which are found both on small recirculating and on blast lymphocytes. The principal effect of substance P on lymphocytes appears to be a stimulating one, both in vitro and in vivo. The in vivo administration of substance P to sheep by acute infusion into cannulated afferent lymphatics of peripheral lymph nodes has been found to stimulate efferent lymph flow and the output into efferent lymph of both small recirculating and blast lymphocytes. We here report that substance P both enhances and prolongs the enhancement of the output of T4 (CD4) lymphocytes from lymph nodes of sheep in vivo. This output-stimulating effect appears to be specific to T4 (CD4) lymphocytes and is associated with a depressant effect on the output of T8 (CD8) and B lymphocytes. The output-stimulating effect on small T4 (CD4) lymphocytes is quite prolonged, lasting in excess of 96 h after a single 50 micrograms acute infusion. A brief post-infusion depression in T4 (CD4) lymphocyte output is associated with an equally brief, but marked, elevation in the output into efferent lymph of the arachidonic acid metabolite, thromboxane B2. The output-stimulating effect of substance P on blast T lymphocytes is confined to the T4 (CD4) blast lymphocytes. Substance P or a similar molecule may be of value when a specific T4 (CD4) lymphocyte output stimulant effect is desired. A single prior (6 days) acute infusion of substance P into a popliteal lymph node via its cannulated afferent lymphatic produced profound changes in the response to nodal drainage area immunization with killed S. muenchen bacteria. The latent period prior to increased antibody production was abolished, as was the standard post-immunization 'shutdown' period of decreased output of lymphocytes into efferent lymph. These changes were accompanied by a marked and progressive increase in antibody production. The findings reported here suggest substance P-induced long-term potentiation (LTP) of the immune response and raise the question of an involvement of substance P as a major mediator of immunological memory.
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PMID:Substance P increases and prolongs increased output of T4 (CD4) lymphocytes from lymph nodes of sheep in vivo: is it a mediator of immunological memory? 170 49

The localization and distribution of neuropeptide Y-like immunoreactivity in the guinea-pig heart were studied by use of immunohistochemical methods. A widespread distribution of immunoreactive processes was observed in all regions of the heart. They occur either singly or together with several other immunoreactive processes and are most often aligned parallel to the myocardial bundles. A dense network of processes is present in the region of both the sinuatrial and atrioventricular nodes and single fibers are occasionally observed to be closely associated with nodal ganglion cells. Positive cell bodies were not seen within the heart. All small, medium and large coronary vessels are surrounded by a dense network of immunoreactive processes. A rich innervation at the media-adventitia junction of the aorta, pulmonary trunk, superior and inferior vena cava was also observed. Comparison of adjacent sections stained with antisera directed to avian pancreatic polypeptide, carboxyl-terminal hexapeptide of pancreatic polypeptide or neuropeptide Y demonstrated a very similar immunoreactive pattern, suggesting that these antisera are reacting with the same or a closely related substance. Likewise, the same immunoreactive patterns were observed in adjacent sections incubated in antiserum to neuropeptide Y or tyrosine hydroxylase, and analysis of elution-restained sections demonstrated that the same processes contain both neuropeptide Y- and tyrosine hydroxylase-like immunoreactivity. Neuropeptide Y- and tyrosine hydroxylase-like immunoreactivity was reduced by the same magnitude after treatment with the sympathetic neurotoxin 6-hydroxydopamine, but it was not affected by the primary sensory neurotoxin capsaicin. Furthermore, the pattern of neuropeptide Y- and tyrosine hydroxylase-like immunoreactivity did not match the staining patterns observed with antisera to vasoactive intestinal polypeptide or substance P or with the acetylcholinesterase staining pattern. In conclusion, neuropeptide Y-like immunoreactivity in the heart and great vessels coexists with that for catecholamines and is likely to originate from sympathetic ganglia.
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PMID:Distribution and colocalization of neuropeptide Y- and tyrosine hydroxylase-like immunoreactivity in the guinea-pig heart. 241 9

A neuroendocrine skin carcinoma cell line MKL-1 has been established from a nodal metastasis in a 26-year-old patient. The line grows as irregularly outlined, loosely packed floating aggregates lacking central necrosis. MKL-1 is hyperdiploid and has a mean doubling time of 120 hours. Xenografts of 2 X 10(7) MKL-1 cells produce tumors in nude mice at 4 to 6 weeks after subcutaneous inoculation. The xenografts were morphologically indistinguishable from the original skin primary and the nodal metastasis. Electron microscopy revealed sparse membrane-bound neurosecretory granules, and conspicuous, paranuclear aggregates of intermediate filaments. Immunohistochemical study showed diffuse and consistent staining with neuron-specific enolase, while bombesin, adrenocorticotrophic hormone, Leu-enkephalin, substance P, and vasoactive intestinal polypeptide displayed heterogeneous and variable expression. Uniform staining of all cells appearing as cytoplasmic fibrils and paranuclear aggregates was noted with antibodies to cytokeratin. Appreciable amounts of cytokeratin polypeptides 8, 18, and 19 and IT protein were seen on two-dimensional gel electrophoresis of cytoskeletal preparations from MKL-1 cells and from tumor-rich frozen sections. Immunostaining also showed coexpression of neurofilaments arranged in paranuclear aggregates; gel electrophoresis and immunoblotting demonstrated the presence in MKL-1 cells of prominent amounts of the small neurofilament polypeptide. Focal expression of desmoplakin was noted in the xenografts. The cells reacted with monoclonal antibodies anti-Leu-7 and anti-Leu-M1 but did not react with antibodies to human lymphocyte antigens (HLA)-A, HLA-B, and HLA-C. Cytogenetic analysis revealed the presence of 3 chromosomally abnormal cell lines with the majority of metaphase cells demonstrating a gain of an isochromosome of the short arm of chromosome 5. Thus, MKL-1 cell line shares several characteristics with small cell neuroendocrine bronchopulmonary carcinoma cell lines but shows distinct cytogenetic abnormalities.
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PMID:Establishment and characterization of a neuroendocrine skin carcinoma cell line. 354 33

Four cases of esophageal carcinoma arising in metaplastic Barrett's epithelium are presented in which multidirectional differentiation was demonstrated by light and/or electron microscopy and immunohistochemistry. All tumors and adjacent mucosa produced both neutral and acidic mucins, as well as one or more hormones indigenous to the gut, including gastrin, bombesin, substance P, somatostatin, and serotonin. Gastrin and somatostatin were the peptides most frequently identified in the tumors, while somatostatin and serotonin predominated in Barrett's epithelium. Ultrastructurally, neurosecretory-type granules, 80-250 nm in diameter, were present in 2 cases; squamous features also were present in one of these cases. One patient displayed hypertrophic osteoarthropathy, which disappeared after the tumor was resected. These cases represent the majority of the Barrett-associated carcinomas in our material. Compared to the "pure" esophageal adenocarcinomas not included in this report, these tumors behaved more aggressively, with wider local involvement and nodal and systemic metastases at the time of presentation. The incidence of multidifferentiation in esophageal carcinomas is not known nor is its possible significance, particularly with regard to tumors arising in metaplastic epithelium. This group may merit further study to detect true differences, if any, between these esophageal carcinomas and their apparently more common counterparts.
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PMID:Carcinoma with multidirectional differentiation arising in Barrett's esophagus. 613 8

The effects of a number of vasoactive and neurotransmitter substances on lymphocyte traffic were studied by assessing their effects on the release of lymphocytes into primary peripheral (popliteal) nodal efferent lymph of sheep following acute infusion into cannulated afferent nodal lymphatics. In a total of 23 experiments, the output of lymphocytes, small and blast, was increased by serotonin, substance P, bombesin, [met]enkephalin, isoprenaline and phenylephrine and was decreased by vasoactive intestinal peptide (VIP), neurotensin and carbachol. Substances whose actions are modulated by prostaglandins and enhanced by prostaglandin synthesis inhibitors and which elevate blood monocyte and nervous tissue levels of cyclic GMP tended to increase lymphocyte traffic through peripheral lymph nodes in sheep in vivo. The opposite effect tended to be produced by substances whose actions require or are associated with prostaglandins or histamine, and which affect blood monocytic cyclic nucleotide levels by elevation of cyclic AMP or depression of cyclic GMP. Pain and inflammation tended to increase lymphocyte traffic, while analgesics and immunomodulators tended to decrease it.
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PMID:Modification of lymphocyte traffic by vasoactive neurotransmitter substances. 614 65

By the use of the peroxidase--antiperoxidase (PAP) technique in the sinus node of several mammalian species, vasoactive intestinal polypeptide (VIP), neurotensin (NT) and substance P (SP) immunoreactive structures were detected. VIP and NT as well as SP immunoreactive fibers were found in close association to the vasculature. While the innervation by SP immunoreactive fibers was restricted to blood vessels, VIP and NT immunoreactive fibers and varicosities were also in contact to nodal cells. Juxtanodal intracardiac ganglia and single intranodal ganglionic cells were supplied by VIP, NT and SP immunoreactive varicosities. In addition, VIP immunoreactive perikarya were present. The results suggest an involvement of VIP, NT and SP in the regulation of sinus node blood flow, in impulse generation as well as in extrinsic and intrinsic cardiac reflex mechanisms.
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PMID:Peptidergic innervation of the mammalian sinus nodes: vasoactive intestinal polypeptide, neurotensin, substance P. 617 50

By the use of the peroxidase-antiperoxidase technique guinea-pig hearts were investigated for the occurrence of neurotensin immunoreactivity. Neurotensin immunoreactive nerve fibers were found in distinct localisations in all hearts studied. In addition, neurotensin immunoreactive fibers were present in the adventitia of the ascending aorta, the aortic arch and the pulmonary trunk. All segments of the coronary vasculature exhibited a dense network of neurotensin immunoreactive fibers. This innervation pattern was most pronounced in the arterial portions. Neurotensin immunoreactive fibers occurred also in close contact with atrial and ventricular muscle cells. A particularly dense innervation by neurotensin immunoreactive fibers was present in the sinu-atrial node and in the atrio-ventricular node. The fibers were associated intimately with blood vessels as well as with nodal cells. In addition, neurotensin immunoreactive fibers were found in intracardiac ganglia. The presence of neurotensin-like immunoreactive material in the guinea-pig heart was demonstrated also by radioimmunoassay. The results of immunohistochemistry and radioimmunoassay were correlated. High performance liquid chromatographic analysis indicated that 20-30% of the total immunoreactivity co-chromatographed with guinea-pig or synthetic neurotensin. Evaluation of consecutive sections revealed different innervation patterns of neurotensin and substance P immunoreactive fibers. The findings suggest a neurotransmitter and/or neuromodulator function of neurotensin in the regulation of coronary circulation, of cardiac impulse generation and conduction, of heart muscle contractility and of cardiac reflex mechanisms. It is speculated that neurotensin might represent the efferent and substance P the afferent part of a cardiac regulatory system.
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PMID:Localization of neurotensin immunoreactive nerve fibers in the guinea-pig heart: evidence derived by immunohistochemistry, radioimmunoassay and chromatography. 618 34

The distribution of vasoactive intestinal polypeptide (VIP) immunoreactivity has been studied in the mammalian heart and compared with that of neurotensin and substance P by use of light-microscopic peroxidase-antiperoxidase immunohistochemistry. VIP-immunoreactive cell bodies are present in intracardiac ganglia in various locations. VIP-immunoreactive nerve fibers predominate in the atria and the conduction system but are rare in the ventricles and occur in cardiac ganglia, endocardium, and epicardium. VIP-ergic nerves supply the coronary vasculature having a preference for the microvasculature and the nodal cells of the sinuatrial node. The large vessels of the heart and periarterial cardiac glomera also receive a VIP-immunoreactive nerve supply. There is partial co-distribution with neurotensin- and substance P-immunoreactive nerve fibers but no co-location in identical nerve fibers is detectable. The VIP-ergic cardiac innervation, which is probably predominantly intrinsic, may stem from postganglionic parasympathetic neurons and is less substantial than the more homogeneous neurotensin-ergic and substance P-ergic nervous supply which is probably extrinsic. The occurrence of an extrinsic VIP-ergic cardiac innervation cannot be excluded however. The differential histotopography of the multitarget cardiac nerves containing the cardiovascular active peptides VIP, neurotensin and substance P may suggest multiple and complex peptide-peptide and peptide-classical transmitter interactions. These may contribute to the regulation of various cardiac functions.
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PMID:Distribution of vasoactive intestinal polypeptide-like immunoreactivity in the mammalian heart. Interrelation with neurotensin- and substance P-like immunoreactive nerves. 620 61

A 55-year-old woman with an ovarian carcinoid presented with intermittent facial and cervical flushing for 10 years, watery diarrhea for 4 years, and abdominal pain without hepatomegaly. Markedly elevated systemic venous and arterial serotonin levels (830 ng/ml; nl = 50-200 ng/ml) were found. The highest serotonin levels were observed in the superior vena caval system, but serotonin as a marker for tumor localization was inaccurate and led to an unproductive neck exploration. The histological pattern of this tumor contained purely insular elements. No hepatic or nodal metastases were identified and the lesion was unilateral. Substance P levels were elevated in the venous drainage of the left ovary and in retrospect correctly localized the ovarian tumor. This peptide may prove to be another carcinoid tumor marker in addition to serotonin and 5-hydroxyindoleacetic acid. Substance P may also be an important mediator of symptoms in patients with carcinoid syndrome.
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PMID:Substance P in the localization of a carcinoid tumor. 620 86


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