PMID- 28336810
OWN - NLM
STAT- MEDLINE
DCOM- 20170731
LR  - 20200930
IS  - 1522-1504 (Electronic)
IS  - 1040-0605 (Print)
IS  - 1040-0605 (Linking)
VI  - 312
IP  - 6
DP  - 2017 Jun 1
TI  - Role of transient receptor potential vanilloid 1 in the modulation of airway 
      smooth muscle tone and calcium handling.
PG  - L812-L821
LID - 10.1152/ajplung.00064.2017 [doi]
AB  - Asthma is a common disorder characterized, in part, by airway smooth muscle (ASM) 
      hyperresponsiveness. Transient receptor potential vanilloid 1 (TRPV1) is a 
      nonselective cation channel expressed on airway nerve fibers that modulates 
      afferent signals, resulting in cough, and potentially bronchoconstriction. In the 
      present study, the TRPV1 transcript was detected by RT-PCR in primary cultured 
      human ASM cells, and the TRPV1 protein was detected in ASM of human trachea by 
      immunohistochemistry. Proximity ligation assays suggest that TRPV1 is expressed 
      in the sarcoplasmic reticulum membrane of human ASM cells in close association 
      with sarco/endoplasmic reticulum Ca(2+)-ATPase-2. In guinea pig tracheal ring 
      organ bath experiments, the TRPV1 agonist capsaicin led to ASM contraction, but 
      this contraction was significantly attenuated by the sodium channel inhibitor 
      bupivacaine (n = 4, P < 0.05) and the neurokinin-2 receptor antagonist GR-159897 
      (n = 4, P < 0.05), suggesting that this contraction is neutrally mediated. 
      However, pretreatment of guinea pig and human ASM in organ bath experiments with 
      the TRPV1 antagonist capsazepine inhibited the maintenance phase of an 
      acetylcholine-induced contraction (n = 4, P < 0.01 for both species). Similarly, 
      capsazepine inhibited methacholine-induced contraction of peripheral airways in 
      mouse precision-cut lung slice (PCLS) experiments (n = 4-5, P < 0.05). Although 
      capsazepine did not inhibit store-operated calcium entry in mouse ASM cells in 
      PCLS (n = 4-7, P = nonsignificant), it did inhibit calcium oscillations (n = 3, P 
      < 0.001). These studies suggest that TRPV1 is expressed on ASM, including the SR, 
      but that ASM TRPV1 activation does not play a significant role in initiation of 
      ASM contraction. However, capsazepine does inhibit maintenance of contraction, 
      likely by inhibiting calcium oscillations.
CI  - Copyright (c) 2017 the American Physiological Society.
FAU - Yocum, Gene T
AU  - Yocum GT
AD  - Department of Anesthesiology, College of Physicians and Surgeons, Columbia 
      University, New York, New York; and gty2102@cumc.columbia.edu.
FAU - Chen, Jun
AU  - Chen J
AD  - Department of Microbiology and Physiological Systems, University of Massachusetts 
      Medical School, Worcester, Massachusetts.
FAU - Choi, Christine H
AU  - Choi CH
AD  - Department of Anesthesiology, College of Physicians and Surgeons, Columbia 
      University, New York, New York; and.
FAU - Townsend, Elizabeth A
AU  - Townsend EA
AD  - Department of Anesthesiology, College of Physicians and Surgeons, Columbia 
      University, New York, New York; and.
FAU - Zhang, Yi
AU  - Zhang Y
AD  - Department of Anesthesiology, College of Physicians and Surgeons, Columbia 
      University, New York, New York; and.
FAU - Xu, Dingbang
AU  - Xu D
AD  - Department of Anesthesiology, College of Physicians and Surgeons, Columbia 
      University, New York, New York; and.
FAU - Fu, Xiao W
AU  - Fu XW
AD  - Department of Anesthesiology, College of Physicians and Surgeons, Columbia 
      University, New York, New York; and.
FAU - Sanderson, Michael J
AU  - Sanderson MJ
AD  - Department of Microbiology and Physiological Systems, University of Massachusetts 
      Medical School, Worcester, Massachusetts.
FAU - Emala, Charles W
AU  - Emala CW
AD  - Department of Anesthesiology, College of Physicians and Surgeons, Columbia 
      University, New York, New York; and.
LA  - eng
GR  - R01 GM065281/GM/NIGMS NIH HHS/United States
GR  - R01 HL122340/HL/NHLBI NIH HHS/United States
GR  - R01 HL103405/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 - 20170323
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 (RNA, Messenger)
RN  - 0 (TRPV Cation Channels)
RN  - 0 (TRPV1 protein, human)
RN  - 0W5ETF9M2K (Methacholine Chloride)
RN  - LFW48MY844 (capsazepine)
RN  - N9YNS0M02X (Acetylcholine)
RN  - S07O44R1ZM (Capsaicin)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Acetylcholine/pharmacology
MH  - Animals
MH  - Calcium/*metabolism
MH  - Capsaicin/analogs & derivatives/pharmacology
MH  - Guinea Pigs
MH  - Humans
MH  - Immunohistochemistry
MH  - Methacholine Chloride/pharmacology
MH  - Mice
MH  - Muscle Contraction/drug effects
MH  - Muscle, Smooth/drug effects/*metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - TRPV Cation Channels/genetics/*metabolism
MH  - Trachea/drug effects/*metabolism
PMC - PMC5495950
OTO - NOTNLM
OT  - asthma
OT  - calcium oscillations
OT  - capsazepine
OT  - organ bath
OT  - precision-cut lung slice
EDAT- 2017/03/25 06:00
MHDA- 2017/08/02 06:00
PMCR- 2018/06/01
CRDT- 2017/03/25 06:00
PHST- 2017/02/14 00:00 [received]
PHST- 2017/03/10 00:00 [revised]
PHST- 2017/03/21 00:00 [accepted]
PHST- 2017/03/25 06:00 [pubmed]
PHST- 2017/08/02 06:00 [medline]
PHST- 2017/03/25 06:00 [entrez]
PHST- 2018/06/01 00:00 [pmc-release]
AID - ajplung.00064.2017 [pii]
AID - L-00064-2017 [pii]
AID - 10.1152/ajplung.00064.2017 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2017 Jun 1;312(6):L812-L821. doi: 
      10.1152/ajplung.00064.2017. Epub 2017 Mar 23.