PMID- 32051870
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2405-8440 (Print)
IS  - 2405-8440 (Electronic)
IS  - 2405-8440 (Linking)
VI  - 6
IP  - 1
DP  - 2020 Jan
TI  - Modification of TRPV4 activity by acetaminophen.
PG  - e03301
LID - 10.1016/j.heliyon.2020.e03301 [doi]
LID - e03301
AB  - N-Acetyl-p-aminophenol (APAP/acetaminophen) is a widely used 
      analgesic/antipyretic with weaker inhibitory effects on cyclooxygenase compared 
      to those of non-steroidal anti-inflammatory drugs. The effect of APAP is mediated 
      by its metabolites, N-arachidonoyl-phenolamine and N-acetyl-p-benzoquinone imine, 
      which activate transient receptor potential (TRP) channels, including TRP 
      vanilloid 1 (TRPV1) and TRP ankyrin 1 (TRPA1) or cannabinoid receptor type 1. 
      However, the exact molecular mechanism underlying the cellular actions of APAP 
      remains unclear. Recently, we observed that APAP promotes cell migration through 
      TRPV4; in this study, we examined the effect of APAP on Ca(2+)-channel activity 
      of TRPV4. In the rat cell line PC12 expressing TRPV4, GSK1016790A (GSK), a TRPV4 
      agonist, stimulated an increase in [Ca(2+)](i); these effects were abrogated by 
      HC-067047 treatment. This GSK-induced Ca(2+) entry through TRPV4 was inhibited by 
      APAP in a dose-dependent manner, whereas APAP alone did not affect [Ca(2+)](i). 
      The specificity of the effect of APAP on TRPV4 was further confirmed using HeLa 
      cells, which lack endogenous TRPV4 but stably express exogenous TRPV4 
      (HeLa-mTRPV4). GSK-induced [Ca(2+)](i) elevation was only observed in HeLa-mTRPV4 
      cells compared to that in the control HeLa cells, indicating the specific action 
      of GSK on TRPV4. APAP dose-dependently suppressed this GSK-induced Ca(2+) entry 
      in HeLa-mTRPV4. However, it is unlikely that the metabolites of APAP were 
      involved in these effects as the reaction in this study was rapid. The results 
      suggest that APAP suppresses the newly identified target TRPV4 without being 
      metabolized and exerts antipyretic/analgesic and/or other effects on 
      TRPV4-related phenomena in the body. The effect of APAP on TRPV4 was opposite to 
      that on TRPV1 or TRPA1, as the latter is activated by APAP.
CI  - (c) 2020 The Author(s).
FAU - Nakagawa, Fumio
AU  - Nakagawa F
AD  - Division of Dental Anesthesiology, Department of Control of Physical Functions, 
      Kyushu Dental University, Kitakyushu, 803-8580, Japan.
AD  - Division of Applied Pharmacology, Department of Health Promotion, Kyushu Dental 
      University, Kitakyushu, 803-8580, Japan.
FAU - Higashi, Sen
AU  - Higashi S
AD  - Division of Applied Pharmacology, Department of Health Promotion, Kyushu Dental 
      University, Kitakyushu, 803-8580, Japan.
FAU - Ando, Eika
AU  - Ando E
AD  - Division of Dental Anesthesiology, Department of Control of Physical Functions, 
      Kyushu Dental University, Kitakyushu, 803-8580, Japan.
FAU - Ohsumi, Tomoko
AU  - Ohsumi T
AD  - Division of Applied Pharmacology, Department of Health Promotion, Kyushu Dental 
      University, Kitakyushu, 803-8580, Japan.
FAU - Watanabe, Seiji
AU  - Watanabe S
AD  - Division of Dental Anesthesiology, Department of Control of Physical Functions, 
      Kyushu Dental University, Kitakyushu, 803-8580, Japan.
FAU - Takeuchi, Hiroshi
AU  - Takeuchi H
AD  - Division of Applied Pharmacology, Department of Health Promotion, Kyushu Dental 
      University, Kitakyushu, 803-8580, Japan.
LA  - eng
PT  - Journal Article
DEP - 20200131
PL  - England
TA  - Heliyon
JT  - Heliyon
JID - 101672560
PMC - PMC7002858
OTO - NOTNLM
OT  - Acetaminophen
OT  - Ca2+
OT  - Cell culture
OT  - Electrophysiology
OT  - Membrane
OT  - Molecular neuroscience
OT  - Nervous system
OT  - Paracetamol
OT  - Physiology
OT  - TRPV4
EDAT- 2020/02/14 06:00
MHDA- 2020/02/14 06:01
PMCR- 2020/01/31
CRDT- 2020/02/14 06:00
PHST- 2019/03/01 00:00 [received]
PHST- 2019/12/15 00:00 [revised]
PHST- 2020/01/22 00:00 [accepted]
PHST- 2020/02/14 06:00 [entrez]
PHST- 2020/02/14 06:00 [pubmed]
PHST- 2020/02/14 06:01 [medline]
PHST- 2020/01/31 00:00 [pmc-release]
AID - S2405-8440(20)30146-8 [pii]
AID - e03301 [pii]
AID - 10.1016/j.heliyon.2020.e03301 [doi]
PST - epublish
SO  - Heliyon. 2020 Jan 31;6(1):e03301. doi: 10.1016/j.heliyon.2020.e03301. eCollection 
      2020 Jan.