PMID- 26453517
OWN - NLM
STAT- MEDLINE
DCOM- 20160502
LR  - 20200930
IS  - 1522-1504 (Electronic)
IS  - 1040-0605 (Print)
IS  - 1040-0605 (Linking)
VI  - 309
IP  - 12
DP  - 2015 Dec 15
TI  - Inositol 1,4,5-trisphosphate activates TRPC3 channels to cause extracellular Ca2+ 
      influx in airway smooth muscle cells.
PG  - L1455-66
LID - 10.1152/ajplung.00148.2015 [doi]
AB  - Transient receptor potential-3 (TRPC3) channels play a predominant role in 
      forming nonselective cation channels (NSCCs) in airway smooth muscle cells 
      (ASMCs) and are significantly increased in their activity and expression in 
      asthmatic ASMCs. To extend these novel findings, we have explored the regulatory 
      mechanisms that control the activity of TRPC3 channels. Our data for the first 
      time reveal that inositol 1,4,5-trisphosphate (IP3), an important endogenous 
      signaling molecule, can significantly enhance the activity of single NSCCs in 
      ASMCs. The analog of diacylglycerol (DAG; another endogenous signaling molecule), 
      1-oleyl-2-acetyl-sn-glycerol (OAG), 1-stearoyl-2-arachidonoyl-sn-glycerol (SAG), 
      and 1-stearoyl-2-linoleoyl-sn-glycerol (SLG) all augment NSCC activity. The 
      effects of IP3 and OAG are fully abolished by lentiviral short-hairpin 
      (sh)RNA-mediated TRPC3 channel knockdown (KD). The stimulatory effect of IP3 is 
      eliminated by heparin, an IP3 receptor (IP3R) antagonist that blocks the 
      IP3-binding site, but not by xestospongin C, the IP3R antagonist that has no 
      effect on the IP3-binding site. Lentiviral shRNA-mediated KD of IP3R1, IP3R2, or 
      IP3R3 does not alter the excitatory effect of IP3. TRPC3 channel KD greatly 
      inhibits IP3-induced increase in intracellular Ca(2+) concentration. IP3R1 KD 
      produces a similar inhibitory effect. TRPC3 channel and IP3R1 KD both diminish 
      the muscarinic receptor agonist methacholine-evoked Ca(2+) responses. Taking 
      these findings together, we conclude that IP3, the important intracellular second 
      messenger, may activate TRPC3 channels to cause extracellular Ca(2+) influx, in 
      addition to opening IP3Rs to induce intracellular Ca(2+) release. This novel 
      extracellular Ca(2+) entry route may play a significant role in mediating 
      IP3-mediated numerous cellular responses in ASMCs and other cells.
CI  - Copyright (c) 2015 the American Physiological Society.
FAU - Song, Tengyao
AU  - Song T
AD  - Center for Cardiovascular Sciences, Albany Medical College, Albany, New York; 
      and.
FAU - Hao, Qiongyu
AU  - Hao Q
AD  - Center for Cardiovascular Sciences, Albany Medical College, Albany, New York; 
      and.
FAU - Zheng, Yun-Min
AU  - Zheng YM
AD  - Center for Cardiovascular Sciences, Albany Medical College, Albany, New York; 
      and.
FAU - Liu, Qing-Hua
AU  - Liu QH
AD  - Center for Cardiovascular Sciences, Albany Medical College, Albany, New York; and 
      Institute for Medical Biology, College of Life Sciences, South-Central University 
      for Nationalities, Wuhan, China.
FAU - Wang, Yong-Xiao
AU  - Wang YX
AD  - Center for Cardiovascular Sciences, Albany Medical College, Albany, New York; and 
      wangy@mail.amc.edu.
LA  - eng
GR  - R01 HL108232/HL/NHLBI NIH HHS/United States
GR  - R01 HL122865/HL/NHLBI NIH HHS/United States
GR  - R01HL071000/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20151009
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 0 (Diglycerides)
RN  - 0 (Inositol 1,4,5-Trisphosphate Receptors)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (TRPC Cation Channels)
RN  - 0 (TRPC3 cation channel)
RN  - 85166-31-0 (Inositol 1,4,5-Trisphosphate)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Binding Sites/drug effects
MH  - Calcium/*metabolism
MH  - Cells, Cultured
MH  - Diglycerides/pharmacology
MH  - Inositol 1,4,5-Trisphosphate/*metabolism
MH  - Inositol 1,4,5-Trisphosphate Receptors/metabolism
MH  - Ion Transport/drug effects
MH  - Mice
MH  - Myocytes, Smooth Muscle/drug effects/*metabolism
MH  - RNA, Small Interfering/genetics
MH  - Respiratory System/drug effects/*metabolism
MH  - TRPC Cation Channels/*metabolism
PMC - PMC4683309
OTO - NOTNLM
OT  - airway myocyte
OT  - ion channel
OT  - signaling pathway
EDAT- 2015/10/11 06:00
MHDA- 2016/05/03 06:00
PMCR- 2016/12/15
CRDT- 2015/10/11 06:00
PHST- 2015/05/07 00:00 [received]
PHST- 2015/10/04 00:00 [accepted]
PHST- 2015/10/11 06:00 [entrez]
PHST- 2015/10/11 06:00 [pubmed]
PHST- 2016/05/03 06:00 [medline]
PHST- 2016/12/15 00:00 [pmc-release]
AID - ajplung.00148.2015 [pii]
AID - L-00148-2015 [pii]
AID - 10.1152/ajplung.00148.2015 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2015 Dec 15;309(12):L1455-66. doi: 
      10.1152/ajplung.00148.2015. Epub 2015 Oct 9.