Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-3-10
pubmed:abstractText
Neuropeptide tachykinins (substance P, neurokinin A, and neurokinin B) are present in peripheral terminals of sensory nerve fibers within the respiratory tract and cause airway contractile responses and hyperresponsiveness in humans and most mammalian species. Three subtypes of neurokinin receptors (NK1R, NK2R, and NK3R) classically couple to Gq protein-mediated inositol 1,4,5-trisphosphate (IP3) synthesis and liberation of intracellular Ca2+, which initiates contraction, but their expression and calcium signaling mechanisms are incompletely understood in airway smooth muscle. All three subtypes were identified in native and cultured human airway smooth muscle (HASM) and were subsequently overexpressed in HASM cells using a human immunodeficiency virus-1-based lentivirus transduction system. Specific NKR agonists {NK1R, [Sar9,Met(O2)11]-substance P; NK2R, [beta-Ala8]-neurokinin A(4-10); NK3R, senktide} stimulated inositol phosphate synthesis and increased intracellular Ca2+ concentration ([Ca2+]i) in native HASM cells and in HASM cells transfected with each NKR subtype. These effects were blocked by NKR-selective antagonists (NK1R, L-732138; NK2R, GR-159897; NK3R, SB-222200). The initial transient and sustained phases of increased [Ca2+]i were predominantly inhibited by the IP3 receptor antagonist 2-aminoethoxydiphenyl borate (2-APB) or the store-operated Ca2+ channel antagonist SKF-96365, respectively. These results show that all three subtypes of NKRs are expressed in native HASM cells and that IP3 levels are the primary mediators of NKR-stimulated initial [Ca2+]i increases, whereas store-operated Ca2+ channels mediate the sustained phase of the [Ca2+]i increase.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/1-(2-(3-(4-methoxyphenyl)propoxy)-4-..., http://linkedlifedata.com/resource/pubmed/chemical/2-aminoethoxydiphenyl borate, http://linkedlifedata.com/resource/pubmed/chemical/Boron Compounds, http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles, http://linkedlifedata.com/resource/pubmed/chemical/Inositol 1,4,5-Trisphosphate, http://linkedlifedata.com/resource/pubmed/chemical/Neurokinin A, http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Neurokinin-1, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Neurokinin-2, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Neurokinin-3, http://linkedlifedata.com/resource/pubmed/chemical/Substance P, http://linkedlifedata.com/resource/pubmed/chemical/neurokinin A (4-10), beta-Ala(8)-, http://linkedlifedata.com/resource/pubmed/chemical/senktide, http://linkedlifedata.com/resource/pubmed/chemical/substance P, Sar(9)-Met(O2)(11)-
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1040-0605
pubmed:author
pubmed:issnType
Print
pubmed:volume
294
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
L523-34
pubmed:dateRevised
2011-5-2
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Expression and coupling of neurokinin receptor subtypes to inositol phosphate and calcium signaling pathways in human airway smooth muscle cells.
pubmed:affiliation
Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, 630 W. 168th St. P&S Box 46, New York, NY 10032, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural