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)

Both intrinsic and extrinsic neurons of the gut respond to mechanical and chemical stimuli by the release of neurotransmitters. We summarize here some of our recent work on the role of vasoactive intestinal polypeptide (VIP), substance P (SP) and neurokinin A (NKA) in the secretory, motor and vascular effects of hydrochloric acid stimulation in the isolated rat duodenal loop and electrical nerve stimulation and mechanical stimulation of the cat colon. Isolated duodenal loops of conscious rats were perfused with isotonic saline, and challenged at hourly intervals with brief exposures to increasing concentrations of HCL. The concentrations of bicarbonate and prostaglandin E2 (PGE2) released from the duodenal mucosa were significantly augmented already by pH 5.0 whereas VIP was significantly augmented at pH 3.0 and the tachykinins SP and NKA at pH 2.0. Continuous electric stimulation of the pelvic nerve in cats at 4 Hz during 1 s with 10 s rest produced a marked release of NKA-LI and SP-LI from the colon to blood. Reflex activation of the pelvic nervae by mechanical stimulation of the anus or rectal distension produced a less pronounced release of NKA-LI and SP-LI from the colon to blood. There was a simultaneous colonic contraction and vasodilation during each nerve stimulation. Close intraarterial infusions of NKA, neurokinin B, SP, neuropeptide K (NPK), eledoisin and physalemin at doses of 0.1-100 pmol/min induced dose-dependent proximal and distal colonic contractions and vasodilation, NKA being the most potent. The effects of the tachykinins were reduced after tetrodotoxin and atropine, but unchanged after treatment with hexamethonium.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Aspects on the role of tachykinins and vasoactive intestinal polypeptide in control of secretion, motility and blood flow in the gut. 195 Jul 87

Explants and cell cultures of embryonic chick ganglia trigeminalia, telencephalon and retina or hippocampus from fetal rats were incubated in maximow chambers in the presence of cyclic AMP and the dipeptide cyclo(Lys-Pro).HCL under various conditions. Maintenance of nerve cells and growth of nerve fibers were observed by morphometrical methods. 1. Cyclo(Lys-Pro).HCL promoted the maintenance of neuroblasts and the growth of nerve fibres in explants of the ganglion trigeminal and retinal cell cultures. The effect depended on the presence of serum in the medium by use of poly-I-lysine substrate. 2. Extern applicated cyclic AMP and the dipeptide SP3-4 = cyclo(Lys-Pro).HCL facilitated neurite growth in PNS cultures. In the presence of the drugs the length of nerve fibers increased for a short term. On CNS explants substance P (SP1-11) and SP3-4 were without effect. Cyclic AMP stimulated the growth of nerve fibers in CNS explants and cell cultures in number and length. 3. Discussed is the effect of SP1-11 and cyclo(Lys-Pro).HCL for competence of nerve fibre regeneration in vitro in relation to increasing cAMP levels, which may then act as an initial second messenger. It is suggested that explants and cell cultures of nervous tissues will be useful as a tool for the further characterisation of factors with neuronotrophic activities.
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PMID:[Effects of cyclic adenosine-3',5'-monophosphate and cyclo(Lys-Pro).HCl neuronotrophic factors in tissue culture]. 282 94

A significant role for the alternative complement pathway in acid aspiration has been demonstrated by the observation that C3 but not C4 genetic knockout mice are protected from permeability edema. Using mast cell-deficient mice (W/Wv), we tested the hypothesis that mast cells mediate complement activation after acid aspiration. Tracheostomy tubes were placed in anesthetized mice and 2 mL/kg 0.1 N HCL was instilled in the trachea. After 4 h, extravasation of 125I-albumin was used to calculate lung vascular permeability. The serum alternative complement pathway hemolytic activity was examined, and lung immunohistochemistry was performed. Lung permeability in W/Wv mice was 62% less than that of mast cell sufficient (+/+) animals and similar to +/+ mice treated with the chymase inhibitor chymostatin (65% decrease). Treatment of +/+ mice with D-PRO2,D-TRP(7,9)-Substance P, an antagonist to the neuropeptide substance P, reduced injury by 66%. Serum complement hemolytic activity was intact in injured w/wv mice and +/+ animals treated with chymostatin or dpdt-sp, but was decreased to 65% in the injured untreated +/+ group. Alveolar C3 deposition was intense in injured untreated +/+ mice but absent in the other groups. We interpret these data to indicate that mast cells mediate complement activation, via chymase degranulation, after acid aspiration. This mast cell activity likely is regulated by the release of substance P.
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PMID:Mast cells mediate complement activation after acid aspiration. 1144 10

We report a unique case of a patient with a neuroendocrine tumor localized to the bone marrow. The patient had a history of hairy cell leukemia, and the neuroendocrine tumor was detected in a bone marrow biopsy specimen obtained to assess response to 2-chlorodeoxyadenosine therapy. The neuroendocrine tumor was present as nodules that replaced approximately 15% of the bone marrow medullary space and was composed of round cells with fine chromatin, indistinct nucleoli, and relatively abundant, granular, eosinophilic cytoplasm. Histochemical stains showed cytoplasmic reactivity with Grimelius and Fontana-Masson stains, and immunohistochemical studies showed positivity for keratin and chromogranin. The histologic, cytochemical, and immunohistochemical features resembled a carcinoid tumor, and metastasis to the bone marrow was considered initially. The patient was asymptomatic without diarrhea, flushing, or cardiac valve disease. Serotonin production, assessed by the measurement of serum 5-hydroxyindoleacetic acid and substance P levels, was normal. Extensive clinical and radiologic work-up and endoscopy of the gastrointestinal tract to detect a primary site other than the bone marrow were negative. Follow-up bone marrow biopsy 7 years after the initial diagnosis was positive for persistent neuroendocrine tumor. The patient has not received any therapy specific for the neuroendocrine tumor and has had no clinical symptoms or evidence of progression after 9 years of clinical follow-up. We suggest that this neuroendocrine tumor may have arisen in the bone marrow.
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PMID:Indolent neuroendocrine tumor involving the bone marrow. A case report with a 9-year follow-up. 1268 82

Nausea and vomiting are considered to be among the most distressing consequences of cytotoxic chemotherapies. Currently, there are several novel 5-HT(3) receptor antagonists for the treatment of chemotherapy-induced nausea and vomiting (CINV), including ondansetron, granisetron, and dolasetron. These agents provide significant improvement in the management of acute emesis but are ineffective at preventing delayed emesis. In 2003, a new 5-HT(3) receptor antagonist, palonosetron HCL (Aloxi), was introduced to the U.S. market. Palonosetron was found to be effective in preventing delayed CINV. Indeed, palonosetron was the first and only 5-HT(3) receptor antagonist approved by the FDA for the prevention of both acute and delayed CINV. More recently, studies on the role of substance P in the emetic process led to the development of aprepitant (Emend) for the prevention of delayed emesis in combination with 5-HT(3) receptor antagonists. Despite these major advances, CINV remains uncontrolled in some patients. Current efforts are focused on treating refractory emesis and include both the clinical evaluation of compounds marketed for other indications and the preclinical evaluation of novel molecules targeting other transmitters in the emetic pathway. Ongoing work in pharmacogenomics has postulated several candidate genes that could be involved in emetic sensitivity and responsiveness to antiemetic therapy. Investigations into the pharmacogenomics of CINV may someday be able to aid in the identification of high risk patients and patients unlikely to respond to conventional therapies.
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PMID:New approaches to chemotherapy-induced nausea and vomiting: from neuropharmacology to clinical investigations. 1703 70