PMID- 10462554
OWN - NLM
STAT- MEDLINE
DCOM- 19990914
LR  - 20190607
IS  - 0026-895X (Print)
IS  - 0026-895X (Linking)
VI  - 56
IP  - 3
DP  - 1999 Sep
TI  - Identification, molecular cloning, expression, and characterization of a
      cysteinyl leukotriene receptor.
PG  - 657-63
AB  - The cysteinyl leukotrienes (CysLTs) have been implicated in the pathophysiology
      of inflammatory disorders, in particular asthma, for which the CysLT receptor
      antagonists pranlukast, zafirlukast, and montelukast, have been introduced
      recently as novel therapeutics. Here we report on the molecular cloning,
      expression, localization, and pharmacological characterization of a CysLT
      receptor (CysLTR), which was identified by ligand fishing of orphan
      seven-transmembrane-spanning, G protein-coupled receptors. This receptor,
      expressed in human embryonic kidney (HEK)-293 cells responded selectively to the 
      individual CysLTs, LTC(4), LTD(4), or LTE(4), with a calcium mobilization
      response; the rank order potency was LTD(4) (EC(50) = 2.5 nM) > LTC(4) (EC(50) = 
      24 nM) > LTE(4) (EC(50) = 240 nM). Evidence was provided that LTE(4) is a partial
      agonist at this receptor. [(3)H]LTD(4) binding and LTD(4)-induced calcium
      mobilization in HEK-293 cells expressing the CysLT receptor were potently
      inhibited by the structurally distinct CysLTR antagonists pranlukast,
      montelukast, zafirlukast, and pobilukast; the rank order potency was pranlukast =
      zafirlukast > montelukast > pobilukast. LTD(4)-induced calcium mobilization in
      HEK-293 cells expressing the CysLT receptor was not affected by pertussis toxin, 
      and the signal appears to be the result of the release from intracellular stores.
      Localization studies indicate the expression of this receptor in several tissues,
      including human lung, human bronchus, and human peripheral blood leukocytes. The 
      discovery of this receptor, which has characteristics of the purported CysLT(1)
      receptor subtype, should assist in the elucidation of the pathophysiological
      roles of the CysLTs and in the identification of additional receptor subtypes.
FAU - Sarau, H M
AU  - Sarau HM
AD  - Department of Pulmonary Pharmacology, SmithKline Beecham Pharmaceuticals, King of
      Prussia, Pennsylvania, USA.
FAU - Ames, R S
AU  - Ames RS
FAU - Chambers, J
AU  - Chambers J
FAU - Ellis, C
AU  - Ellis C
FAU - Elshourbagy, N
AU  - Elshourbagy N
FAU - Foley, J J
AU  - Foley JJ
FAU - Schmidt, D B
AU  - Schmidt DB
FAU - Muccitelli, R M
AU  - Muccitelli RM
FAU - Jenkins, O
AU  - Jenkins O
FAU - Murdock, P R
AU  - Murdock PR
FAU - Herrity, N C
AU  - Herrity NC
FAU - Halsey, W
AU  - Halsey W
FAU - Sathe, G
AU  - Sathe G
FAU - Muir, A I
AU  - Muir AI
FAU - Nuthulaganti, P
AU  - Nuthulaganti P
FAU - Dytko, G M
AU  - Dytko GM
FAU - Buckley, P T
AU  - Buckley PT
FAU - Wilson, S
AU  - Wilson S
FAU - Bergsma, D J
AU  - Bergsma DJ
FAU - Hay, D W
AU  - Hay DW
LA  - eng
SI  - GENBANK/AF133266
PT  - Journal Article
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (Membrane Proteins)
RN  - 0 (Receptors, Leukotriene)
RN  - 0 (Virulence Factors, Bordetella)
RN  - 73836-78-9 (Leukotriene D4)
RN  - AJT72OTM42 (cysteinyl leukotriene receptor 2)
RN  - EC 2.4.2.31 (Pertussis Toxin)
RN  - LRF7RW46ID (leukotriene D4 receptor)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - Binding Sites
MH  - Biological Transport/drug effects
MH  - Calcium/metabolism
MH  - Cells, Cultured
MH  - Cloning, Molecular
MH  - Humans
MH  - Leukotriene D4/pharmacology
MH  - *Membrane Proteins
MH  - Molecular Sequence Data
MH  - Pertussis Toxin
MH  - Receptors, Leukotriene/*genetics/metabolism
MH  - Signal Transduction/drug effects
MH  - Virulence Factors, Bordetella/pharmacology
EDAT- 1999/08/27 00:00
MHDA- 1999/08/27 00:01
CRDT- 1999/08/27 00:00
PHST- 1999/08/27 00:00 [pubmed]
PHST- 1999/08/27 00:01 [medline]
PHST- 1999/08/27 00:00 [entrez]
AID - 10.1124/mol.56.3.657 [doi]
PST - ppublish
SO  - Mol Pharmacol. 1999 Sep;56(3):657-63. doi: 10.1124/mol.56.3.657.