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)

Neuropeptides have recently been implicated in regulation of normal and neoplastic cell growth. Substance K is a neurotransmittor candidate that has been identified as a mitogen for smooth muscle cells and fibroblasts. However, the ability to respond to stimulation with substance K declines rapidly in cells serum-starved for more than 24 h and in parallel with a decrease in the intracellular level of myc-gene transcripts. Contrarily, myc-transformed cells, that inspite of a decrease demonstrated a high level of myc mRNA after 48 h in serum-free medium, maintained their ability to initiate DNA synthesis when stimulated with substance K. The results suggest that the intracellular signal of substance K-induced DNA synthesis interacts with the myc protein.
 ...
PMID:DNA synthesis induced by the neuropeptide substance K correlates to the level of myc-gene transcripts. 242 45

Peptides released from peripheral nerve endings in mammals, including the tachykinin substance P (SP) and vasoactive intestinal polypeptide (VIP), are potent mediators of smooth muscle and vascular functions. Significant neurophysiological activities of SP and VIP include the transmission of nociceptive and interneuron excitatory signals, respectively. SP has been shown to modulate distinct immediate hypersensitivity responses by stimulating the generation of arachidonic acid-derived mediators from mucosal mast cells but not basophils. Functions of mononuclear and polymorphonuclear leukocytes that characterize the inflammatory response and that are altered by SP include chemotaxis, lysosomal enzyme release, and phagocytic activities. The effects of SP on cell-mediated immunity are largely stimulatory, in that synthesis of DNA, protein, and immunoglobulin by mature T and B lymphocytes, respectively, is significantly enhanced at nanomolar concentrations of the neuropeptide. Functionally relevant receptors for SP on T lymphocytes have been demonstrated by cell sorter and radioligand-binding techniques, and the lymphocyte membrane proteins that comprise the SP receptor are currently being isolated and purified to homogeneity. The characterization of the structure of the SP lymphocyte receptor and identification of the receptor gene will permit detailed analyses of the molecular interactions between the immune and nervous systems.
 ...
PMID:Substance P and immunoregulation. 243 63

Synthetic oligonucleotides were used to screen a rat striatal cDNA library for sequences corresponding to the tachykinin peptides substance P and neurokinin A. The cDNA library was constructed from RNA isolated from the rostral portion of the rat corpus striatum, the site of striatonigral cell bodies. Two types of cDNAs were isolated and defined by restriction enzyme analysis and DNA sequencing to encode both substance P and neurokinin A. The two predicted preprotachykinin protein precursors (130 and 115 amino acids in length) differ from each other by a pentadecapeptide sequence between the two tachykinin sequences, and both precursors possess appropriate processing signals for substance P and neurokinin A production. The presence of a third preprotachykinin mRNA of minor abundance in rat striatum was established by S1 nuclease protection experiments. This mRNA encodes a preprotachykinin of 112 amino acids containing substance P but not neurokinin A. These three mRNAs are derived from one rat gene as a result of differential RNA processing; thus, this RNA processing pattern further increases the diversity of products that can be generated from the preprotachykinin gene.
 ...
PMID:Three rat preprotachykinin mRNAs encode the neuropeptides substance P and neurokinin A. 243 92

When rat parotid explants were cultured on siliconized lens paper floating on chemically defined 199 medium, all of sialagogues tested increased ornithine decarboxylase activity, which was roughly proportional to the amylase released into the culture medium. S-Adenosylmethionine decarboxylase and DNA synthesis were also induced by isoproterenol, methoxamine, carbachol and pilocarpine, but not by serotonin or substance P. The increases of the two decarboxylase activities and DNA synthesis were observed in vivo in mouse parotid gland after repeated injections of carbachol or pilocarpine. These results indicate that both adrenergic and cholinergic sialagogues stimulate the syntheses of polyamines and DNA in murine parotid gland.
 ...
PMID:Effects of sialagogues on the syntheses of polyamines and DNA in murine parotid gland. 243 23

We have deleted cDNA sequences encoding portions of the carboxy-terminal end of a human type I epidermal keratin K14, and examined the molecular consequences of forcing the expression of these mutants in simple epithelial and squamous cell carcinoma lines. To follow the expression of our mutant products in transfected cells, we have tagged the 3' end of the K14 coding sequence with a sequence encoding an antigenic domain of the neuropeptide substance P. Using DNA transfection and immunohistochemistry (with an antibody against substance P), we have identified a collection of mutants that have a wide range of morphological effects on the endogenous keratin filament networks of transfected cells. Mutants that are missing most of the nonhelical carboxy-terminal domain of K14 incorporate into the endogenous keratin filaments without any visible perturbations on the network. In contrast, mutants that are missing as few as 10 of the 310 amino acids of the central alpha-helical domain of the polypeptide cause gross alterations in the keratin network. In some cases, the entire cytoskeletal network of keratins was disrupted, leaving no evidence of 8-nm filaments. These results reveal the existence of a dynamic exchange between newly synthesized subunits and preexisting keratin filaments.
 ...
PMID:The expression of mutant epidermal keratin cDNAs transfected in simple epithelial and squamous cell carcinoma lines. 244 74

The cellular distribution of preprotachykinin A messenger RNA in the bovine nervous system was investigated by in situ hybridization and its tissue distribution by Northern and dot blotting. The latter results were compared with the levels of substance P-like immunoreactivity as determined by radio-immunoassay. The highest levels of preprotachykinin A messenger RNA were found in striatum and trigeminal ganglion, medium levels in retina and lower levels in hypothalamus, spinal cord, pituitary gland and adrenal medulla. The cellular localization of preprotachykinin A messenger RNA was obtained in striatum and trigeminal ganglion using either single-stranded DNA or complementary RNA probes labelled with 32P, 35S or 3H. Specific labelling of small trigeminal ganglion neurones and of medium-sized striatal nerve cells was observed with probes in the anti-messenger RNA sense orientation. Only background labelling was obtained with probes in the messenger RNA sense orientation. The technique was further validated by the demonstration that the same cells in the trigeminal ganglion were labelled by both in situ hybridization and immunohistochemistry. The present findings allow an unambiguous identification of the cellular sites of synthesis of preprotachykinin A messenger RNA; in situ hybridization should also prove a useful technique for investigating the regulation of neuropeptide biosynthesis at the cellular level.
 ...
PMID:The cellular localization of preprotachykinin A messenger RNA in the bovine nervous system. 244 1

Patients with medullary thyroid carcinomas (MTC) were analyzed according to age, sex, and tumor stage. In addition, the MTC were screened for the predominant histologic pattern, immunocytochemical spectrum (60 tumors), and DNA content (DNA cytophotometry and DNA flow cytometry, 25 tumors). These findings were correlated with follow-up data available for 45 of these patients. Forty-eight percent of the tumors revealed a polygonal cell pattern, whereas 22% showed spindle-cell predominance. All tumors contained cytokeratin, chromogranin A, and calcitonin (CT). Calcitonin gene-related peptide (CGRP) was present in 92%, carcinoembryonic antigen (CEA) in 77%, neuron-specific enolase (NSE) in 75%, and vimentin in 53% of cases. Positivity for neurotensin, somatostatin, neurofilaments, bombesin, and alpha human chorionic gonadotropin (a-hCG) and serotonin ranged between 3% and 27%. All MTC were negative for substance P, adrenocorticotropic hormone (ACTH), thyroglobulin (TG), or S-100 protein. Local recurrences and regional lymph node metastases revealed identical staining patterns as the primaries. Prognosis of MTC was found not to be related to histologic features (dominant architectural pattern, cellular shape, presence of amyloid deposits) or immunocytochemical pattern. Instead, survival was significantly correlated to age, sex, and stage of disease. The best prognosis was seen in women younger than 40 years and revealing an early stage of disease. DNA measurements added valuable information in assessing the prognosis of MTC.
 ...
PMID:Prognostic factors in medullary thyroid carcinomas. Survival in relation to age, sex, stage, histology, immunocytochemistry, and DNA content. 244 25

The effects of substance P and substance K, which are coexpressed in the same mRNA as a beta-preprotachykinin in peripheral tissues and released in the inflammatory lesion of the skin, were examined on epidermal proliferation using spontaneously transformed mouse epidermal cell line (Pam 212 cells). Substance P stimulated the synthesis of DNA of Pam 212 cells in the medium containing 2%-10% fetal calf serum (FCS). Stimulation of DNA synthesis was dose dependent if the cells were cultured in the medium containing 2% FCS (quiescent condition). This effect was inhibited by spantide. In a serum-free medium, substance P had no effect on keratinocyte proliferation. In contrast, substance K, which shares a common amino acid sequence with substance P on its C-terminal, did not affect DNA synthesis of Pam 212 cells in either medium condition. Substance P released in inflammation may stimulate epidermal proliferation.
 ...
PMID:Effects of substance P and substance K on the growth of cultured keratinocytes. 245 Jan 47

In the search for a more potent bombesin antagonist, we found [D-Arg1,D-Phe5,D-Trp7,9,Leu11]substance P to be effective in mouse fibroblasts and to inhibit the growth of small cell lung cancer, a tumor that secretes bombesin-like peptides that may act as autocrine growth factors. In murine Swiss 3T3 cells, [D-Arg1,D-Phe5,D-Trp7,9,Leu11]substance P proved to be a bombesin antagonist as judged by the following criteria: (i) inhibition of DNA synthesis induced by gastrin-releasing peptide and other bombesin-like peptides; (ii) inhibition of 125I-labeled gastrin-releasing peptide binding to the bombesin/gastrin-releasing peptide receptor; (iii) reduction in cross-linking of the Mr 75,000-85,000 protein putatively a component of the bombesin/gastrin-releasing peptide receptor; (iv) blocking of early cellular events that precede mitogenesis--calcium mobilization and inhibition of epidermal growth factor binding. [D-Arg1,D-Phe5,D-Trp7,9,Leu11]substance P was 5-fold more potent than the antagonist [D-Arg1,D-Pro2,D-Trp7,9,Leu11]substance P. [D-Arg1,D-Phe5,D-Trp7,9,Leu11]substance P also inhibits mitogenesis induced by vasopressin but not that induced by a variety of other mitogens. Both antagonists reversibly inhibited the growth of small cell lung cancer in vitro in a concentration-dependent manner. Peptide antagonists could, therefore, have far-reaching therapeutic implications.
 ...
PMID:[D-Arg1,D-Phe5,D-Trp7,9,Leu11]substance P, a potent bombesin antagonist in murine Swiss 3T3 cells, inhibits the growth of human small cell lung cancer cells in vitro. 245 Mar 49

Many experiments have demonstrated that the nervous and immune systems interact in a bidirectional fashion. Neuropeptides, including substance P, have been shown to modulate lymphocyte DNA, RNA and immunoglobulin synthesis in vitro and to play a role in inflammatory and hypersensitivity disease states. However, the role of substance P as an immunomodulator in vivo is uncertain and there is only indirect evidence of this effect obtained in vitro. Therefore, we have assessed the effect of substance in vivo on DNA and immunoglobulin synthesis by murine splenic and Peyer's patch lymphocytes after the continuous administration via a miniosmotic pump of substance P in vivo. Substance P administered in this fashion increased cell proliferation of lymphocytes isolated from both organs. Immunoglobulin synthesis was also increased and in a relatively isotype-specific manner. IgA synthesis was most affected, IgM synthesis less so and IgG synthesis was not changed significantly. These effects of substance P on lymphocytes in vivo are similar to its effects on cell proliferation and immunoglobulin synthesis when cells are exposed to this peptide in vitro. These results provide direct evidence that neuropeptides (substance P) may modulate lymphocyte function in vivo and that neuropeptides should be incorporated into the conceptual framework of immune regulation.
 ...
PMID:In vivo immunomodulation by the neuropeptide substance P. 245 90


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>