PMID- 25460045
OWN - NLM
STAT- MEDLINE
DCOM- 20150825
LR  - 20181202
IS  - 1873-3913 (Electronic)
IS  - 0898-6568 (Linking)
VI  - 27
IP  - 2
DP  - 2015 Feb
TI  - Thyronamine induces TRPM8 channel activation in human conjunctival epithelial 
      cells.
PG  - 315-25
LID - S0898-6568(14)00361-1 [pii]
LID - 10.1016/j.cellsig.2014.11.015 [doi]
AB  - 3-Iodothyronamine (T1AM), an endogenous thyroid hormone (TH) metabolite, induces 
      numerous responses including a spontaneously reversible body temperature decline. 
      As such an effect is associated in the eye with increases in basal tear flow and 
      thermosensitive transient receptor potential melastatin 8 (TRPM8) channel 
      activation, we determined in human conjunctival epithelial cells (IOBA-NHC) if 
      T1AM also acts as a cooling agent to directly affect TRPM8 activation at a 
      constant temperature. RT-PCR and quantitative real-time PCR (qPCR) along with 
      immunocytochemistry probed for TRPM8 gene and protein expression whereas 
      functional activity was evaluated by comparing the effects of T1AM with those of 
      TRPM8 mediators on intracellular Ca(2+) ([Ca(2+)]i) and whole-cell currents. 
      TRPM8 gene and protein expression was evident and icilin (20muM), a TRPM8 agonist, 
      increased Ca(2+) influx as well as whole-cell currents whereas BCTC (10muM), a 
      TRPM8 antagonist, suppressed these effects. Similarly, either temperature 
      lowering below 23 degrees C or T1AM (1muM) induced Ca(2+) transients that were blocked by 
      this antagonist. TRPM8 activation by both 1microM T1AM and 20muM icilin prevented 
      capsaicin (CAP) (20muM) from inducing increases in Ca(2+) influx through TRP 
      vanilloid 1 (TRPV1) activation, whereas BCTC did not block this response. CAP 
      (20muM) induced a 2.5-fold increase in IL-6 release whereas during exposure to 
      20muM capsazepine this rise was completely blocked. Similarly, T1AM (1muM) 
      prevented this response. Taken together, T1AM like icilin is a cooling agent 
      since they both directly elicit TRPM8 activation at a constant temperature. 
      Moreover, there is an inverse association between changes in TRPM8 and TRPV1 
      activity since these cooling agents blocked both CAP-induced TRPV1 activation and 
      downstream rises in IL-6 release.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Khajavi, Noushafarin
AU  - Khajavi N
AD  - Charite-Universitatsmedizin Berlin, Campus Virchow-Klinikum, Klinik fur 
      Augenheilkunde, Augustenburger Platz 1, D-13353 Berlin, Germany.
FAU - Reinach, Peter S
AU  - Reinach PS
AD  - Biological Sciences, SUNY College of Optometry, New York, NY 10036, USA; School 
      of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou 325027, PR 
      China.
FAU - Slavi, Nefeli
AU  - Slavi N
AD  - Biological Sciences, SUNY College of Optometry, New York, NY 10036, USA.
FAU - Skrzypski, Marek
AU  - Skrzypski M
AD  - Department of Animal Physiology and Biochemistry, Poznan University of Life 
      Sciences, 60-637 Poznan, Poland.
FAU - Lucius, Alexander
AU  - Lucius A
AD  - Charite-Universitatsmedizin Berlin, Campus Virchow-Klinikum, Klinik fur 
      Augenheilkunde, Augustenburger Platz 1, D-13353 Berlin, Germany.
FAU - Strauss, Olaf
AU  - Strauss O
AD  - Charite-Universitatsmedizin Berlin, Campus Virchow-Klinikum, Klinik fur 
      Augenheilkunde, Augustenburger Platz 1, D-13353 Berlin, Germany.
FAU - Kohrle, Josef
AU  - Kohrle J
AD  - Institut fur Experimentelle Endokrinologie, Charite-Universitatsmedizin Berlin, 
      Augustenburger Platz 1, D-13353 Berlin, Germany.
FAU - Mergler, Stefan
AU  - Mergler S
AD  - Charite-Universitatsmedizin Berlin, Campus Virchow-Klinikum, Klinik fur 
      Augenheilkunde, Augustenburger Platz 1, D-13353 Berlin, Germany. Electronic 
      address: stefan.mergler@charite.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141121
PL  - England
TA  - Cell Signal
JT  - Cellular signalling
JID - 8904683
RN  - 0 (3-iodothyronamine)
RN  - 0 (Interleukin-6)
RN  - 0 (Pyrimidinones)
RN  - 0 (RNA, Messenger)
RN  - 0 (TRPM Cation Channels)
RN  - 0 (TRPM8 protein, human)
RN  - 0 (TRPV Cation Channels)
RN  - 0 (TRPV1 protein, human)
RN  - 0 (Thyronines)
RN  - CS70PZQ4QJ (icilin)
RN  - S07O44R1ZM (Capsaicin)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Calcium/metabolism
MH  - Capsaicin/pharmacology
MH  - Cell Line
MH  - Conjunctiva/cytology/physiology
MH  - Epithelial Cells/cytology/drug effects/physiology
MH  - Humans
MH  - Interleukin-6/metabolism
MH  - Membrane Potentials/*drug effects
MH  - Patch-Clamp Techniques
MH  - Pyrimidinones/pharmacology
MH  - RNA, Messenger/metabolism
MH  - TRPM Cation Channels/genetics/*metabolism
MH  - TRPV Cation Channels/metabolism
MH  - Thyronines/*pharmacology
OTO - NOTNLM
OT  - Calcium transient receptor potential melastatin 8 channel
OT  - Human conjunctival epithelium
OT  - Intracellular Ca(2+), thyronamine, interleukin (IL)-6, dry eye syndrome, planar 
      patch-clamp technique
EDAT- 2014/12/03 06:00
MHDA- 2015/08/26 06:00
CRDT- 2014/12/03 06:00
PHST- 2014/09/16 00:00 [received]
PHST- 2014/10/31 00:00 [revised]
PHST- 2014/11/12 00:00 [accepted]
PHST- 2014/12/03 06:00 [entrez]
PHST- 2014/12/03 06:00 [pubmed]
PHST- 2015/08/26 06:00 [medline]
AID - S0898-6568(14)00361-1 [pii]
AID - 10.1016/j.cellsig.2014.11.015 [doi]
PST - ppublish
SO  - Cell Signal. 2015 Feb;27(2):315-25. doi: 10.1016/j.cellsig.2014.11.015. Epub 2014 
      Nov 21.