Linked Life Data

11705452

Source:http://linkedlifedata.com/resource/pubmed/id/11705452

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2001-11-13
pubmed:abstractText
We sought to clone and characterize the murine cysteinyl-leukotriene D(4) receptor (mCysLT(1)R) to complement our studies with leukotriene-deficient mice. A cDNA, cloned from trachea mRNA by reverse transcriptase-polymerase chain reaction, has two potential initiator ATG codons that would encode for polypeptides of 352 and 339 amino acids, respectively. These two potential forms, predicted to be seven transmembrane-spanning domain proteins, have 87% amino acid identity with the human CysLT(1) receptor (hCysLT(1)R). Membrane fractions of Cos-7 cells transiently expressing the short mCysLT(1)R demonstrated high affinity and specific binding for leukotriene D(4) (LTD(4), K(d) = 0.25 +/- 0.04 nM). In competition binding experiments, LTD(4) was the most potent competitor (K(i) = 0.8 +/- 0.2 nM) followed by LTE(4) and LTC(4) (K(i) = 86.6 +/- 24.5 and 100.1 +/- 17.1 nM, respectively) and LTB(4) (K(i) > 1.5 microM). Binding of LTD(4) was competitively inhibited by the specific CysLT(1) receptor antagonists MK-571 [(+)-3-(((3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl) ((3-(dimethylamino)-3-oxopropyl)thio)methyl)thio)propanoic acid], pranlukast (Onon), and zafirlukast (Accolate), while the CysLT(1)/CysLT(2) receptor antagonist BAY-u9773 [6(R)-(4'-carboxyphenylthio)-5(S)-hydroxy-7(E),9(E),11(Z),14(Z)-eicosatetrenoic acid] was 1000 times less potent than LTD(4). In transiently transfected HEK293-T cells expressing either the long or short form of mCysLT(1)R, LTD(4) induced an increase of intracellular calcium. In Xenopus laevis melanophores transiently expressing either isoform, LTD(4) induced the dispersion of pigment granules, consistent with the activation by LTD(4) of a G(alphaq) (calcium) pathway. Functional elucidation of mCysLT(1)R properties as described here will enable further experiments to clarify the selective role of LTD(4) in murine models of inflammation and asthma.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
62
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1193-200
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11705452-Aequorin, pubmed-meshheading:11705452-Amino Acid Sequence, pubmed-meshheading:11705452-Animals, pubmed-meshheading:11705452-Base Sequence, pubmed-meshheading:11705452-Cells, Cultured, pubmed-meshheading:11705452-Cloning, Molecular, pubmed-meshheading:11705452-DNA, Complementary, pubmed-meshheading:11705452-Humans, pubmed-meshheading:11705452-Luminescent Measurements, pubmed-meshheading:11705452-Melanophores, pubmed-meshheading:11705452-Membrane Proteins, pubmed-meshheading:11705452-Mice, pubmed-meshheading:11705452-Molecular Sequence Data, pubmed-meshheading:11705452-Radioligand Assay, pubmed-meshheading:11705452-Receptors, Leukotriene, pubmed-meshheading:11705452-Sequence Analysis, Protein, pubmed-meshheading:11705452-Sequence Homology, Amino Acid, pubmed-meshheading:11705452-Xenopus laevis
pubmed:year
2001
pubmed:articleTitle
Molecular cloning and functional characterization of murine cysteinyl-leukotriene 1 (CysLT(1)) receptors.
pubmed:affiliation
Center for Experimental Therapeutics, 814 BRB II/III, University of Pennsylvania, 421 Curie Boulevard, Philadelphia, PA 19104-6160, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't