NCBI
PubMed A service of the U.S. National Library of Medicine
and the National Institutes of Health
My NCBI
[Sign In] [Register]










All Databases
PubMed
Nucleotide
Protein
Genome
Structure
OMIM
PMC
Journals
Books
PubMed
Search





Go Clear
Limits
Preview/Index
History
Clipboard
Details
Display
20
for
AbstractPlus
Show
Sort By
All: 1 Review: 0 Click to change filter selection through MyNCBI.
1: Ann Surg. 2007 Mar;245(3):408-14.
Links
Substance P regulates migration in rat intestinal
epithelial cells.
Turner DJ, Martin PC, Rao JN, Greenspon J, Zou T, Bass BL, Wang JY,
Strauch ED.
Cell Biology Group, Department of Surgery, University of Maryland School of
Medicine, Baltimore, MD, USA. dturner@smail.umaryland.edu
OBJECTIVE: The current study examined the effect of substance P (SP) upon
intestinal epithelial cells and the mechanistic details of this interaction.
SUMMARY BACKGROUND DATA: Intestinal epithelial cells must be capable
of migration to reseal mucosal wounds for several vital intestinal functions. This
process is incompletely understood; however, recent evidence implicates the
neurotransmitter SP in this process. METHODS: Normal rat intestinal epithelial
cells (IEC-6 cells) were studied to identify the presence of the SP receptor (NK-1
subtype) and then exposed to physiologic doses of SP and antagonists to assess
for increased migration. RESULTS: Examination IEC-6 cells revealed the
presence of the SP receptor. Wounding of these cells followed by subsequent
exposure to SP (10 mol/L) resulted in increased migration. Similarly, SP-induced
increases in intracellular calcium concentration and actomyosin stress fiber
formation. These effects were all blocked through specific NK-1 receptor
antagonists. CONCLUSIONS: These results indicate that SP stimulates intestinal
epithelial migration and increases in calcium concentration. These data support a
beneficial role for SP in the maintenance of intestinal mucosal homeostasis.
PMID: 17435548 [PubMed - indexed for MEDLINE]
PMCID: PMC1877018
Related Links





Display
20
Substance P induces intestinal wound healing via fibroblasts--evidence for
a TGF-beta-dependent effect. [Int J Colorectal Dis. 2007]
Differentiated intestinal epithelial cells exhibit increased migration
through polyamines and myosin II. [Am J Physiol. 1999]
NF-kappaB regulates intestinal epithelial cell and bile salt-induced
migration after injury. [Ann Surg. 2003]
Activation of K(+) channels and increased migration of differentiated
intestinal epithelial cells after wounding. [Am J Physiol Cell Physiol.
2002]
Neurokinin-1 receptor (NK-1R) expression is induced in human colonic
epithelial cells by proinflammatory cytokines and mediates proliferation in
response to substance P. [J Cell Physiol. 2003]
 » See all Related Articles...
AbstractPlus
Sort By
Show




Write to the Help Desk
NCBI | NLM | NIH
Department of Health & Human Services
Privacy Statement | Freedom of Information Act | Disclaimer
J Cell Physiol. 2003 Oct;197(1):30-41.
Links
Neurokinin-1 receptor (NK-1R) expression is
induced in human colonic epithelial cells by
proinflammatory cytokines and mediates
proliferation in response to substance P.
Goode T, O'Connor T, Hopkins A, Moriarty D, O'Sullivan GC, Collins JK,
O'Donoghue D, Baird AW, O'Connell J, Shanahan F.
Department of Medicine, National University of Ireland, Cork, Ireland.
We have previously shown that the receptor for substance P (SP), neurokinin-1
receptor (NK-1R), is a marker of human mucosal but not peripheral mononuclear
cells. In the present study, we investigate NK-1R expression in the human colonic
mucosa in vivo, particularly in the epithelial cells. We investigate the influence of
proinflammatory Th1 cytokines and SP on expression and function of NK-1R in
colonic epithelial cells in vitro. Using in situ hybridization to detect NK-1R
mRNA, and immunohistochemistry to detect NK-1R protein, colonic epithelial
cells were found to express NK-1R in vivo. In contrast, colon epithelial cell lines
(Caco-2, HT29, SW620, T84) were negative for NK-1R mRNA and protein.
However, stimulation with a proinflammatory cytokine cocktail containing IFNgamma, TNF-alpha, and IL-1beta, caused induction of NK-1R expression.
Expression of NK-1R in human colonic epithelial cells in vivo may therefore
reflect cytokine conditioning by the mucosal microenvironment. SP did not alter
ion transport in monolayers of cytokine-treated T84 cells. While SP stimulated
epithelial ion transport in colonic mucosae ex vivo, this was not a direct effect of
SP on the epithelial cells, and appeared to be neurally mediated. However, SP
(10(-10)-10(-8) M) elicited a dose-dependent proliferative effect on cytokinestimulated, but not unstimulated, SW620 cells. Proliferation of the epithelial cells
in response to SP was mediated specifically via cytokine-induced NK-1R, since
an NK-1R-specific antagonist (Spantide 1) completely blocked SP-mediated
proliferation in the cytokine-treated cells. Our results therefore demonstrate that
proinflammatory cytokines induce expression of NK-1R in human colonic
epithelial cell lines, and that SP induces proliferation of the epithelial cells via
cytokine-induced NK-1R. Copyright 2003 Wiley-Liss, Inc.
PMID: 12942538 [PubMed - indexed for MEDLINE
Lab Invest. 2003 May;83(5):731-42.Links
Neurokinin-1 receptor expression and its potential
effects on tumor growth in human pancreatic
cancer.
Friess H, Zhu Z, Liard V, Shi X, Shrikhande SV, Wang L, Lieb K, Korc M,
Palma C, Zimmermann A, Reubi JC, Büchler MW.
Department of General Surgery, University of Heidelberg, Germany.
helmut_friess@med.uni-heidelberg.de
The neurokinin-1 receptor (NK-1R) and its ligand substance P (SP) are involved
in the pathogenesis of certain neural tumors. Because nerves are significantly
altered in pancreatic cancer, evidence for alteration of this pathway in human
pancreatic cancer was sought. Expression of NK-1R was analyzed by real-time
quantitative RT-PCR, in situ hybridization, immunohistochemistry, and Western
blot analysis in normal human pancreatic and pancreatic cancer tissue samples
and in pancreatic cancer cell lines. Furthermore, the influence of SP analogs and
of the NK-1R antagonist MEN 11467 on pancreatic cancer cell growth was
analyzed by sulforhodamine B (SRB) assay. By real-time quantitative RT-PCR,
NK-1R mRNA was increased 36.7-fold (p < 0.001) in human pancreatic cancer
samples compared with normal controls. Enhanced NK-1R expression levels were
not related to tumor grade but were associated with advanced tumor stage and
poorer prognosis. By in situ hybridization and immunohistochemistry, NK-1R
mRNA and immunoreactivity were only occasionally weakly present in acinar
and ductal cells in the normal pancreas. In contrast, moderate to strong NK-1R
mRNA signals and immunoreactivity were present in most cancer cells. By
Western blot analysis, NK-1R was increased 26-fold (p < 0.01) in pancreatic
cancer samples in comparison to normal controls. NK-1R mRNA was detected in
five pancreatic cancer cell lines by real-time quantitative RT-PCR, with the
highest levels in CAPAN-1 cells and the lowest in ASPC-1 cells. SP analogs
stimulated pancreatic cancer cell growth, depending on the NK-1R expression
level, and this effect could be blocked by a selective NK-1R antagonist. These
findings illustrate that the NK-1R pathway is activated in human pancreatic
cancer and has the potential to contribute to cancer cell growth, thus suggesting
the existence of a neuro-cancer cell interaction in vivo.
PMID: 12746482 [PubMed - indexed for MEDLINE]
Clin Diagn Lab Immunol. 2000 May;7(3):371-6.
Links
Differential expression of neurokinin-1 receptor by
human mucosal and peripheral lymphoid cells.
Goode T, O'Connell J, Ho WZ, O'Sullivan GC, Collins JK, Douglas SD,
Shanahan F.
Department of Medicine, National University of Ireland, Cork, Ireland.
Substance P (SP) has been implicated in peripheral and mucosal
neuroimmunoregulation. However, confusion remains regarding immunocyte
expression of the receptor for SP, neurokinin-1 receptor (NK-1R), and whether
there is differential NK-1R expression in the mucosal versus the peripheral
immune system. In the same assay systems, we examined the expression of NK1R in human lamina propria mononuclear cells (LPMC), peripheral blood
mononuclear cells (PBMC), peripheral blood lymphocytes (PBL), monocytes, and
monocyte-derived macrophages (MDM). Using standard reverse transcription
(RT)-PCR, mRNA expression of both the long and the short isoforms of the NK1R was evident in LPMC but not in PBMC, PBL, monocytes, or MDM. However,
by using nested RT-PCR NK-1R mRNA expression was detected in PBMC, PBL,
monocytes, and MDM. This level of expression was found to represent one NK1R mRNA transcript in >1,000 cells. In contrast, by using competitive RT-PCR
we demonstrate that LPMC express a more biologically significant level of eight
NK-1R mRNA transcripts per cell. Flow cytometric detection of NK-1R
expression at the protein level was evident in LPMC but not in PBMC. These
findings illustrate the extreme sensitivity of nested RT-PCR and the advantages of
competitive RT-PCR in comparative studies of receptor expression in different
cell populations. This study suggests that, under normal conditions, readily
detectable expression of NK-1R in human mononuclear cells occurs at the
mucosal level rather than in the peripheral circulation.
PMID: 10799448 [PubMed - indexed for MEDLINE]
J Neurosci Res. 2006 Nov 15;84(7):1588-96.
Links
Morphine upregulates functional expression of
neurokinin-1 receptor in neurons.
Wan Q, Douglas SD, Wang X, Kolson DL, O'Donnell LA, Ho WZ.
Division of Allergy and Immunology, Joseph Stokes Jr. Research Institute at The
Children's Hospital of Philadelphia, Department of Pediatrics, Philadelphia,
Pennsylvania.
Neuronkinin-1 receptor (NK-1R), the neuropeptide substance P (SP) preferring
receptor, is highly expressed in areas of the central nervous system (CNS) that are
especially implicated in depression, anxiety, and stress. Repeated exposure to
opioids may sensitize neuronal systems involved in stress response. We examined
the effects of morphine, the principal metabolite of heroin, on the functional
expression of NK-1R in the cortical neurons. NK-1R and mu-opioid receptor
(MOR) are co-expressed in the cortical neurons. Morphine enhanced NK-1R
expression in the cortical neurons at both the mRNA and protein levels. The
upregulated NK-1R by morphine had functional activity, because morphinetreated cortical neurons had greater SP-induced Ca(2+) mobilization than
untreated neurons. Blocking opioid receptors on the cortical neurons by
naltrexone or CTAP (a mu-opioid receptor antagonist) abolished the morphine
action. Investigation of the mechanism(s) responsible for the morphine action
showed that morphine activated NK-1R promoter and induced the
phosphorylation of p38 MAPK protein in the cortical neurons. These in vitro data
provide a plausible cellular mechanism for opioid-mediated neurological
disorders.
PMID: 16983662