PMID- 24360935
OWN - NLM
STAT- MEDLINE
DCOM- 20141014
LR  - 20181202
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 724
DP  - 2014 Feb 5
TI  - Pranlukast inhibits renal epithelial cyst progression via activation of 
      AMP-activated protein kinase.
PG  - 67-76
LID - S0014-2999(13)00940-0 [pii]
LID - 10.1016/j.ejphar.2013.12.013 [doi]
AB  - Cysteinyl leukotriene receptor 1 (CysLT1 receptor) antagonists were found to 
      inhibit chloride secretion in human airway epithelial cells. Since chloride 
      secretion in renal epithelial cells, which shares common mechanisms with airway 
      epithelial cells, plays important roles in renal cyst progression in polycystic 
      kidney disease (PKD), this study was aimed to investigate effects of drugs acting 
      as CysLT1 receptor antagonists on renal cyst progression and its underlying 
      mechanisms. Effects of CysLT1 receptor antagonists on renal cyst growth and 
      formation were determined using Madine Darby canine kidney (MDCK) cyst models. 
      Mechanisms of actions of CysLT1 receptor antagonists were determined using 
      short-circuit current measurement, assays of cell viability and cell 
      proliferation, and immunoblot analysis of signaling proteins. Of the three drugs 
      acting as CysLT1 receptor antagonists (montelukast, pranlukast and zafirlukast) 
      tested, pranlukast was the most promising drug that inhibited MDCK cyst growth 
      and formation without affecting cell viability. Its effect was independent of the 
      inhibition of CysLT1 receptors. Instead, it reduced cAMP-activated chloride 
      secretion and proliferation of MDCK cells in an AMP-activated protein kinase 
      (AMPK)-dependent manner and had no effect on CFTR protein expression. 
      Interestingly, pranlukast enhanced AMPK activation via 
      calcium/calmodulin-dependent protein kinase kinase beta (CaMKKbeta) with consequent 
      activation of acetyl-CoA carboxylase (ACC) and suppression of mammalian target of 
      rapamycin (mTOR) pathway. These results indicate that pranlukast retards renal 
      epithelial cyst progression by inhibiting cAMP-activated chloride secretion and 
      cell proliferation via CaMKKbeta-AMPK-mTOR pathway. Therefore, pranlukast represents 
      a class of known drugs that may have potential utility in PKD treatment.
CI  - Copyright (c) 2013 Elsevier B.V. All rights reserved.
FAU - Pathomthongtaweechai, Nutthapoom
AU  - Pathomthongtaweechai N
AD  - Department of Physiology and Research Center of Transport Protein for Medical 
      Innovation, Faculty of Science, Mahidol University, Rama 6 Rd., Rajathevi, 
      Bangkok 10400, Thailand.
FAU - Soodvilai, Sunhapas
AU  - Soodvilai S
AD  - Department of Physiology and Research Center of Transport Protein for Medical 
      Innovation, Faculty of Science, Mahidol University, Rama 6 Rd., Rajathevi, 
      Bangkok 10400, Thailand.
FAU - Chatsudthipong, Varanuj
AU  - Chatsudthipong V
AD  - Department of Physiology and Research Center of Transport Protein for Medical 
      Innovation, Faculty of Science, Mahidol University, Rama 6 Rd., Rajathevi, 
      Bangkok 10400, Thailand.
FAU - Muanprasat, Chatchai
AU  - Muanprasat C
AD  - Department of Physiology and Research Center of Transport Protein for Medical 
      Innovation, Faculty of Science, Mahidol University, Rama 6 Rd., Rajathevi, 
      Bangkok 10400, Thailand. Electronic address: chatchai.mua@mahidol.ac.th.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131217
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Chlorides)
RN  - 0 (Chromones)
RN  - 0 (Leukotriene Antagonists)
RN  - 0 (Receptors, Leukotriene)
RN  - 126880-72-6 (Cystic Fibrosis Transmembrane Conductance Regulator)
RN  - 1F7A44V6OU (Colforsin)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - LRF7RW46ID (leukotriene D4 receptor)
RN  - TB8Z891092 (pranlukast)
SB  - IM
MH  - AMP-Activated Protein Kinases/*metabolism
MH  - Animals
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Chlorides/metabolism
MH  - Chromones/*pharmacology
MH  - Colforsin/pharmacology
MH  - Cystic Fibrosis Transmembrane Conductance Regulator/metabolism
MH  - Cysts/drug therapy/*metabolism
MH  - Dogs
MH  - Epithelial Cells/*drug effects/metabolism/pathology
MH  - Kidney/pathology
MH  - Leukotriene Antagonists/*pharmacology
MH  - Madin Darby Canine Kidney Cells
MH  - Polycystic Kidney Diseases
MH  - Receptors, Leukotriene/metabolism
OTO - NOTNLM
OT  - AMPK
OT  - CFTR
OT  - Polycystic kidney disease
OT  - Pranlukast
OT  - mTOR
EDAT- 2013/12/24 06:00
MHDA- 2014/10/15 06:00
CRDT- 2013/12/24 06:00
PHST- 2013/10/22 00:00 [received]
PHST- 2013/12/01 00:00 [revised]
PHST- 2013/12/04 00:00 [accepted]
PHST- 2013/12/24 06:00 [entrez]
PHST- 2013/12/24 06:00 [pubmed]
PHST- 2014/10/15 06:00 [medline]
AID - S0014-2999(13)00940-0 [pii]
AID - 10.1016/j.ejphar.2013.12.013 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2014 Feb 5;724:67-76. doi: 10.1016/j.ejphar.2013.12.013. Epub 
      2013 Dec 17.