PMID- 10391245
OWN - NLM
STAT- MEDLINE
DCOM- 19990721
LR  - 20181201
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 399
IP  - 6738
DP  - 1999 Jun 24
TI  - Characterization of the human cysteinyl leukotriene CysLT1 receptor.
PG  - 789-93
AB  - The cysteinyl leukotrienes-leukotriene C4(LTC4), leukotriene D4(LTD4) and
      leukotriene E4(LTE4)-are important mediators of human bronchial asthma.
      Pharmacological studies have determined that cysteinyl leukotrienes activate at
      least two receptors, designated CysLT1 and CysLT2. The CysLT1-selective
      antagonists, such as montelukast (Singulair), zafirlukast (Accolate) and
      pranlukast (Onon), are important in the treatment of asthma. Previous biochemical
      characterization of CysLT1 antagonists and the CysLT1 receptor has been in
      membrane preparations from tissues enriched for this receptor. Here we report the
      molecular and pharmacological characterization of the cloned human CysLT1
      receptor. We describe the functional activation (calcium mobilization) of this
      receptor by LTD4 and LTC4, and competition for radiolabelled LTD4 binding to this
      receptor by the cysteinyl leukotrienes and three structurally distinct classes of
      CysLT1-receptor antagonists. We detected CysLT1-receptor messenger RNA in spleen,
      peripheral blood leukocytes and lung. In normal human lung, expression of the
      CysLT1-receptor mRNA was confined to smooth muscle cells and tissue macrophages. 
      Finally, we mapped the human CysLT1-receptor gene to the X chromosome.
FAU - Lynch, K R
AU  - Lynch KR
AD  - Department of Pharmacology, University of Virginia Health Sciences Center,
      Charlottesville 22908, USA.
FAU - O'Neill, G P
AU  - O'Neill GP
FAU - Liu, Q
AU  - Liu Q
FAU - Im, D S
AU  - Im DS
FAU - Sawyer, N
AU  - Sawyer N
FAU - Metters, K M
AU  - Metters KM
FAU - Coulombe, N
AU  - Coulombe N
FAU - Abramovitz, M
AU  - Abramovitz M
FAU - Figueroa, D J
AU  - Figueroa DJ
FAU - Zeng, Z
AU  - Zeng Z
FAU - Connolly, B M
AU  - Connolly BM
FAU - Bai, C
AU  - Bai C
FAU - Austin, C P
AU  - Austin CP
FAU - Chateauneuf, A
AU  - Chateauneuf A
FAU - Stocco, R
AU  - Stocco R
FAU - Greig, G M
AU  - Greig GM
FAU - Kargman, S
AU  - Kargman S
FAU - Hooks, S B
AU  - Hooks SB
FAU - Hosfield, E
AU  - Hosfield E
FAU - Williams, D L Jr
AU  - Williams DL Jr
FAU - Ford-Hutchinson, A W
AU  - Ford-Hutchinson AW
FAU - Caskey, C T
AU  - Caskey CT
FAU - Evans, J F
AU  - Evans JF
LA  - eng
SI  - GENBANK/AF119711
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Leukotriene Antagonists)
RN  - 0 (Membrane Proteins)
RN  - 0 (Receptors, Leukotriene)
RN  - 73836-78-9 (Leukotriene D4)
RN  - AJT72OTM42 (cysteinyl leukotriene receptor 2)
RN  - LRF7RW46ID (leukotriene D4 receptor)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - Blotting, Northern
MH  - COS Cells
MH  - Chromosome Mapping
MH  - Cloning, Molecular
MH  - Humans
MH  - Leukotriene Antagonists
MH  - Leukotriene D4
MH  - Lung/metabolism
MH  - Macrophages, Alveolar/metabolism
MH  - *Membrane Proteins
MH  - Molecular Sequence Data
MH  - Muscle, Smooth/metabolism
MH  - Receptors, Leukotriene/chemistry/genetics/*physiology
MH  - Tissue Distribution
MH  - Transfection
MH  - X Chromosome
MH  - Xenopus laevis
EDAT- 1999/07/03 10:00
MHDA- 2001/03/23 10:01
CRDT- 1999/07/03 10:00
PHST- 1999/07/03 10:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/07/03 10:00 [entrez]
AID - 10.1038/21658 [doi]
PST - ppublish
SO  - Nature. 1999 Jun 24;399(6738):789-93. doi: 10.1038/21658.