PMID- 30483120
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 9
DP  - 2018
TI  - TRPM8 Activation via 3-Iodothyronamine Blunts VEGF-Induced Transactivation of 
      TRPV1 in Human Uveal Melanoma Cells.
PG  - 1234
LID - 10.3389/fphar.2018.01234 [doi]
LID - 1234
AB  - In human uveal melanoma (UM), tumor enlargement is associated with increases in 
      aqueous humor vascular endothelial growth factor-A (VEGF-A) content that induce 
      neovascularization. 3-Iodothyronamine (3-T(1)AM), an endogenous thyroid hormone 
      metabolite, activates TRP melastatin 8 (TRPM8), which blunts TRP vanilloid 1 
      (TRPV1) activation by capsaicin (CAP) in human corneal, conjunctival epithelial 
      cells, and stromal cells. We compare here the effects of TRPM8 activation on 
      VEGF-induced transactivation of TRPV1 in an UM cell line (92.1) with those in 
      normal primary porcine melanocytes (PM) since TRPM8 is upregulated in melanoma. 
      Fluorescence Ca(2+)-imaging and planar patch-clamping characterized functional 
      channel activities. CAP (20 muM) induced Ca(2+) transients and increased 
      whole-cell currents in both the UM cell line and PM whereas TRPM8 agonists, 100 
      muM menthol and 20 muM icilin, blunted such responses in the UM cells. VEGF (10 
      ng/ml) elicited Ca(2+) transients and augmented whole-cell currents, which were 
      blocked by capsazepine (CPZ; 20 muM) but not by a highly selective TRPM8 blocker, 
      AMTB (20 muM). The VEGF-induced current increases were not augmented by CAP. Both 
      3-T(1)AM (1 muM) and menthol (100 muM) increased the whole-cell currents, whereas 
      20 muM AMTB blocked them. 3-T(1)AM exposure suppressed both VEGF-induced Ca(2+) 
      transients and increases in underlying whole-cell currents. Taken together, 
      functional TRPM8 upregulation in UM 92.1 cells suggests that TRPM8 is a potential 
      drug target for suppressing VEGF induced increases in neovascularization and UM 
      tumor growth since TRPM8 activation blocked VEGF transactivation of TRPV1.
FAU - Walcher, Lia
AU  - Walcher L
AD  - Klinik fur Augenheilkunde, Charite - Universitatsmedizin Berlin, Corporate Member 
      of Freie Universitat Berlin, Berlin Institute of Health, Humboldt-Universitat zu 
      Berlin, Berlin, Germany.
FAU - Budde, Clara
AU  - Budde C
AD  - Klinik fur Augenheilkunde, Charite - Universitatsmedizin Berlin, Corporate Member 
      of Freie Universitat Berlin, Berlin Institute of Health, Humboldt-Universitat zu 
      Berlin, Berlin, Germany.
FAU - Bohm, Arina
AU  - Bohm A
AD  - Klinik fur Augenheilkunde, Charite - Universitatsmedizin Berlin, Corporate Member 
      of Freie Universitat Berlin, Berlin Institute of Health, Humboldt-Universitat zu 
      Berlin, Berlin, Germany.
FAU - Reinach, Peter S
AU  - Reinach PS
AD  - School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, 
      China.
FAU - Dhandapani, Priyavathi
AU  - Dhandapani P
AD  - MDC Buch, Berlin, Germany.
FAU - Ljubojevic, Nina
AU  - Ljubojevic N
AD  - Klinik fur Augenheilkunde, Charite - Universitatsmedizin Berlin, Corporate Member 
      of Freie Universitat Berlin, Berlin Institute of Health, Humboldt-Universitat zu 
      Berlin, Berlin, Germany.
FAU - Schweiger, Markus W
AU  - Schweiger MW
AD  - Klinik fur Augenheilkunde, Charite - Universitatsmedizin Berlin, Corporate Member 
      of Freie Universitat Berlin, Berlin Institute of Health, Humboldt-Universitat zu 
      Berlin, Berlin, Germany.
FAU - von der Waydbrink, Henriette
AU  - von der Waydbrink H
AD  - Klinik fur Augenheilkunde, Charite - Universitatsmedizin Berlin, Corporate Member 
      of Freie Universitat Berlin, Berlin Institute of Health, Humboldt-Universitat zu 
      Berlin, Berlin, Germany.
FAU - Reimers, Ilka
AU  - Reimers I
AD  - Klinik fur Augenheilkunde, Charite - Universitatsmedizin Berlin, Corporate Member 
      of Freie Universitat Berlin, Berlin Institute of Health, Humboldt-Universitat zu 
      Berlin, Berlin, Germany.
FAU - Kohrle, Josef
AU  - Kohrle J
AD  - Institut fur Experimentelle Endokrinologie, Charite - Universitatsmedizin Berlin, 
      Corporate Member of Freie Universitat Berlin, Berlin Institute of Health, 
      Humboldt-Universitat zu Berlin, Berlin, Germany.
FAU - Mergler, Stefan
AU  - Mergler S
AD  - Klinik fur Augenheilkunde, Charite - Universitatsmedizin Berlin, Corporate Member 
      of Freie Universitat Berlin, Berlin Institute of Health, Humboldt-Universitat zu 
      Berlin, Berlin, Germany.
LA  - eng
PT  - Journal Article
DEP - 20181113
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC6243059
OTO - NOTNLM
OT  - 3-iodothyronamine
OT  - Intracellular Ca2+
OT  - transient receptor potential melastatin 8
OT  - transient receptor potential vanilloid 1 channel
OT  - uveal melanoma
OT  - vascular endothelial growth factor
EDAT- 2018/11/30 06:00
MHDA- 2018/11/30 06:01
PMCR- 2018/11/13
CRDT- 2018/11/29 06:00
PHST- 2018/06/20 00:00 [received]
PHST- 2018/10/11 00:00 [accepted]
PHST- 2018/11/29 06:00 [entrez]
PHST- 2018/11/30 06:00 [pubmed]
PHST- 2018/11/30 06:01 [medline]
PHST- 2018/11/13 00:00 [pmc-release]
AID - 10.3389/fphar.2018.01234 [doi]
PST - epublish
SO  - Front Pharmacol. 2018 Nov 13;9:1234. doi: 10.3389/fphar.2018.01234. eCollection 
      2018.