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)

Substance P is a member of the tachykinin peptide family and participates in the regulation of diverse biological processes. The polymerase chain reaction and conventional library screening were used to isolate a complementary DNA (cDNA) encoding the rat substance P receptor from brain and submandibular gland. By homology analysis, this receptor belongs to the G protein-coupled receptor superfamily. The receptor cDNA was expressed in a mammalian cell line and the ligand binding properties of the encoded receptor were pharmacologically defined by Scatchard analysis and tachykinin peptide displacement as those of a substance P receptor. The distribution of the messenger RNA for this receptor is highest in urinary bladder, submandibular gland, striatum, and spinal cord, which is consistent with the known distribution of substance P receptor binding sites. Thus, this receptor appears to mediate the primary actions of substance P in various brain regions and peripheral tissues.
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PMID:Molecular characterization of a functional cDNA encoding the rat substance P receptor. 215 52

The effects of the vasoactive perivascular neuropeptides calcitonin gene-related peptide (CGRP), neurokinin A (NKA), neuropeptide Y (NPY), and vasoactive intestinal polypeptide (VIP) on proliferation of cultured human umbilical vein endothelial cells (HUVECs) were investigated. CGRP was shown to increase both cell number and DNA synthesis, whereas NKA, NPY, and VIP were ineffective. 125I-labeled CGRP was shown to bind to HUVECs and this binding was displaced by addition of unlabeled CGRP, suggesting the existence of specific CGRP receptors. The effect of CGRP on formation of adenosine 3',5'-cyclic monophosphate (cAMP) and inositol phosphates (InsP), two intracellular messengers known to be involved in regulation of cell proliferation, was investigated. CGRP stimulated cAMP formation but was without effect on the formation of InsP. Proliferation, as well as cAMP formation, was also stimulated by cholera toxin. Basic fibroblast growth factor stimulated growth without affecting cAMP or InsP formation, whereas thrombin, which increased InsP formation, did not stimulate proliferation. We thus suggest that CGRP may act as a local factor stimulating proliferation of endothelial cells; that the mechanism of action is associated with cAMP formation; and that this effect of CGRP may be important for formation of new vessels during physiological and pathophysiological events such as ischemia, inflammation, and wound healing.
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PMID:Calcitonin gene-related peptide stimulates proliferation of human endothelial cells. 215 44

Neurokinin A (substance K) is a peptide neurotransmitter of the tachykinin family with potential as a major mediator in human airway and gastrointestinal tissues. Neurokinin A acts via a receptor (the NK-2 receptor) believed to be localized on smooth muscle cells and pharmacologically coupled to a GTP-binding protein. To characterize the human NK-2 receptor, we prepared a partial cDNA from human tracheal RNA using the polymerase chain reaction with oligonucleotide primers derived from the bovine NK-2 receptor cDNA sequence (Masu, Y., Nakayama, K., Tamaki, H., Harada, Y., Kuno, M., Nakanishi, S. (1987) Nature 329, 836-838). This partial human NK-2 receptor cDNA was used to screen a human genomic DNA library and yielded a clone, NGNK-2, of approximately 25 kilobases. Analysis of NGNK-2 indicates that it contains the entire coding sequence of the NK-2 receptor as well as 5'- and 3'-flanking sequences. The gene is organized with five exons interrupted by four introns. The complete sequence of the exons and the intron-exon junctions was determined, as were the transcription initiation site and the 3'-polyadenylation signal. Analysis of EcoRI digests of genomic DNA from human-mouse cell hybrids indicates a single gene for the human NK-2 receptor localized to chromosome 10. Sequence analysis of exons 1 and 5, where major differences occur between the human and animal species, provided information for polymerase chain reaction primers which allowed us to prepare full-length cDNA for the human NK-2 receptor. The protein predicted from the gene sequence is extended by 14 amino acids at the COOH terminus compared to the bovine and 9 residues compared to the rat molecules. The seven membrane-spanning regions are encoded by exons 1-4 and none is interrupted by introns. These regions are highly conserved among the species studied, suggesting stringent evolutionary control over these molecules.
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PMID:The human neurokinin A (substance K) receptor. Molecular cloning of the gene, chromosome localization, and isolation of cDNA from tracheal and gastric tissues. 184 90

Neurokinin A (NKA), a neuropeptide belonging to the tachykinin family, induced c-fos proto-oncogene mRNA expression in serum-deprived L6J1 rat skeletal myoblasts in vitro. The marked increase reached maximal levels after 15 to 30 min. In contrast to this, c-jun and c-myc proto-oncogene expression were only slightly induced, with peak levels after 30 min. NKA did not stimulate DNA synthesis or cell proliferation in serum-deprived L6J1 myoblasts. We demonstrate a relationship between NKA treatment and induction of c-fos, c-jun and c-myc mRNA expression in serum-deprived L6J1 rat myoblasts. The results on DNA synthesis and cell proliferation indicate that the induced proto-oncogene expression alone is not enough to induce a cellular response to NKA. Possible mechanisms of action are discussed.
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PMID:Neurokinin A induces c-fos, c-jun, and c-myc expression in L6 rat myoblasts. 217 88

Neurokinin A, a member of the tachykinin family of neuropeptides, has been identified as a mitogen for cultured smooth muscle cells. Tachykinin-induced DNA synthesis has previously been shown to be mediated by a receptor-specific mechanism and to correlate with accumulation of phosphatidylinositol 4,5-bisphosphate breakdown products. In the present experiments, we have studied intracellular pH and expression of the proto-oncogenes c-myc, c-jun and c-fos in smooth muscle cells exposed to mitogenic concentrations of neurokinin A. Growth-arrested smooth muscle cells stimulated with neurokinin A responded with an amiloride-sensitive intracellular alkalinization, indicating Na+/H+ antiport activation. c-myc and c-jun mRNA expression was only slightly elevated by neurokinin A, while c-fos expression underwent a more pronounced increase. Maximal levels of c-fos transcripts were found after 15 min and 30 min following neurokinin A stimulation. The results demonstrate that neuropeptides may influence proto-oncogene expression in smooth muscle cells and suggest a mechanism by which peripheral neurons may modulate differentiation and growth of these cells.
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PMID:Neurokinin A induces expression of the c-fos, c-jun, and c-myc genes in rat smooth muscle cells. 217 99

We examined the effect of vasoactive intestinal peptide, substance P, and somatostatin on concanavalin A (1 microgram/ml)-induced lymphocyte proliferation and immunoglobulin (IgA, IgM, and IgG) synthesis by cells from spleens, Peyer's patches, and mesenteric lymph nodes. These neuropeptides (10(-7) to 10(-12) M) modulated immune responses in a dose-dependent manner. For a comparative study, neuropeptides were used at 10(-8) M concentration. Both vasoactive intestinal peptide and somatostatin significantly decreased DNA synthesis (30 to 50%), whereas substance P increased synthesis (40%) in lymphocytes from all organs tested. IgA synthesis was significantly altered by all of the neuropeptides tested, whereas IgM synthesis was less affected and IgG synthesis was virtually unchanged. Somatostatin inhibited IgA (20 to 50%) and IgM (10 to 30%) synthesis in lymphocytes from all three organs. Substance P increased IgA synthesis in mesenteric lymph nodes (50%), spleens (70%), and Peyer's patches (300%). It also increased IgM synthesis in Peyer's patches (20%) and spleens (30%), but was without effect on IgM synthesis in mesenteric lymph nodes. Vasoactive intestinal peptide increased the IgA response in mesenteric lymph nodes (20%) and spleens (30%), but inhibited IgA synthesis in lymphocytes from Peyer's patches (60%). Interestingly, in Peyer's patches, IgM synthesis was increased by vasoactive intestinal peptide (80%), whereas it was unchanged in mesenteric lymph nodes and spleen. Thus, not only did these neuropeptides have different effects on the production of different immunoglobulin isotypes, but their effect was also organ-specific. Because neuropeptides which are abundant in the intestine can modulate IgA and other immunoglobulin synthesis in vitro, they may play a significant regulatory role in mucosal immune responses in vivo.
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PMID:Differential effects of vasoactive intestinal peptide, substance P, and somatostatin on immunoglobulin synthesis and proliferations by lymphocytes from Peyer's patches, mesenteric lymph nodes, and spleen. 241 14

This study was aimed at providing new knowledge on the pathology of Infantile Hypertrophic Pyloric Stenosis (IHPS) with some recently developed techniques and hence contributing to the understanding of its unsolved aetiology. Biopsy specimens of the pylorus were obtained from 15 children with IHPS at operation and 6 normal children at autopsy and compared as follows: (a) the presence or absence of muscle hyperplasia in IHPS was studied with special chromatin stain. No mitotic figures were observed in 10,000 cells screened; (b) Using the Schneider procedure, specimens from IHPS showed 1.47 +/- 0.09 mg DNA/g wet tissue (mean +/- SEM) compared with 2.38 +/- 0.18 mg DNA/g wet tissue in normal, defining the magnitude of muscular hypertrophy objectively to be in the region of 1.62 times normal; (c) Cholinesterase staining revealed adequate density of ganglia with no gross distortion of morphology in IHPS; (d) Immunocytochemical study with the marker neurone-specific-enolase confirmed that ganglia in IHPS were mature; (e) Immunocytochemical study with substance P revealed rich peptidergic innervation of the normal pylorus and a relative paucity in IHPS. This was interpreted as a phenomenon of exhaustion of substance P-neurones in IHPS. In conclusion, IHPS is a true muscle hypertrophy with little or no hyperplasia. The cholinergic ganglia are adequate and neural elements in general are sufficiently mature. The novel idea of possible disturbances of peptidergic innervation contributing to its aetiology has received some support.
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PMID:Observations and perspectives of the pathology and possible aetiology of infantile hypertrophic pyloric stenosis--a histological, biochemical, histochemical and immunocytochemical study. 241 61

The synthetic peptide [D-Arg1,D-Pro2,D-Trp7,9,Leu1]substance P inhibits the stimulation of DNA synthesis induced in Swiss 3T3 cells by bombesin or vasopressin, but not that induced by a wide range of other growth factors and mitogens. The stimulation induced by 10 pM-3 nM-bombesin is inhibited by 1-30 microM-antagonist in a manner consistent with competition at the bombesin receptor. The inhibition by the antagonist of the stimulation induced by vasopressin suggests a previously unrecognized interaction of the antagonist with vasopressin receptors. The antagonist should be useful in studies of cell proliferation both in vivo and in vitro.
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PMID:A peptide that inhibits the mitogenic stimulation of Swiss 3T3 cells by bombesin or vasopressin. 241 11

A vector system has been designed for obtaining high yields of polypeptides synthesized in Escherichia coli. Multiple copies of a synthetic gene encoding the neuropeptide substance P (SP) (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2) have been linked and fused to the lacZ gene. Each copy of the SP gene was flanked by codons for methionine to create sites for cleavage by cyanogen bromide (CNBr). The isolated multimeric SP fusion protein was converted to monomers of SP analog, each containing a carboxyl-terminal homoserine lactone (Hse-lactone) residue (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Hse-lactone), upon treatment with CNBr in formic acid. The Hse-lactone moiety was subjected to chemical modifications to produce an SP Hse amide. This method permits synthesis of peptide amide analogs and other peptide derivatives by combining recombinant DNA techniques and chemical methods.
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PMID:Multiple-copy genes: production and modification of monomeric peptides from large multimeric fusion proteins. 241 4

While vasopressin and peptides of the bombesin family bind to different receptors in quiescent Swiss 3T3 cells, the antagonist [D-Arg1,D-pro2,D-Trp7,9,Leu11] substance P blocks the specific binding of both (3H) vasopressin and 125I-gastrin-releasing peptide to these cells. In addition, the antagonist inhibits the mobilization of Ca2+ and induction of DNA synthesis by vasopressin. These results indicate that [D-Arg1,D-Pro2,D-Trp7,9,Leu11] substance P has the ability to interact with the receptors for three structurally unrelated peptide hormones.
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PMID:A substance P antagonist also inhibits specific binding and mitogenic effects of vasopressin and bombesin-related peptides in Swiss 3T3 cells. 242 43


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